KR20130055043A - Novel peptides that stimulate human neutrophils - Google Patents

Abstract

PURPOSE: A novel peptide is provided to promote intracellular calcium ion release through activation of phospholipase C and to act on leukocytes, and to promote reactive oxygen generation. CONSTITUTION: A peptide contains an amino acid sequence selected from the group consisting of sequence numbers 1-3. The peptide regulates activity of neutrophil. The peptide induces increase of intracellular calcium ions, stimulates cell chemotactic motion, and specifically acts on leukocytes. The peptide of sequence number 2 or 3 induces superoxide generation in human neutrophil. The peptide of sequence number 1 or 3 act on FPR1(formyl peptide receptor 1). The peptide of sequence number 2 act on FPR2(formyl peptide receptor 2). A pharmaceutical composition contains pharmaceutically effective amount of the peptide.

Description

Novel peptides that stimulate human neutrophils

The present invention relates to novel peptides, and more particularly to novel peptides that regulate the activity of neutrophils.

Neutrophils play an important role in the regulation of the innate immune response. Neutrophils move to the site of infection when the pathogens are infected, which effectively detects pathogens, and plays a key role in treating inflammatory diseases caused by infections by killing the pathogens. Removal of these infectious bacteria is known to be mediated by reactive oxygen produced by neutrophil activation. As such, activation of neutrophils, which play key functions in the innate immune response, can be induced by extracellular stimulation.

Simplifying neutrophil stimulation, after neutrophil activating ligand is attached to a specific receptor on the neutrophil membrane, guanosine triphosphate (GTP) is activated, which in turn is phosphatidyl-inositol-4,5-biphosphate (phosphatidyl-inositol-4,5-biphosphate, PIP ₂ ) and certain phospholipase C (PLC). Phospholipase C is phosphatidyl-inositol-4,5-biphosphate to inositol-1,4,5-triphosphate (inositol-1,4,5-triphosphate, IP ₃ ) and diacylglycerol (DG) Catalyzes hydrolysis. IP ₃ stimulates the release of calcium ions (Ca ²⁺ ) from intracellular storage.

Neutrophil activity can be induced by a variety of stimuli, such as chemotactic factors, which bind to specific cell surface receptors, intracellular calcium ion mobility, cell migration, exocytosis, adhesion (adhesion), and production of reactive oxygen species.

There are a variety of active substances that can regulate the activity of neutrophils, including interleukin-8, but small molecule peptides, including N-formyl-Met-Leu-Phe has been reported limited.

The present inventors aim to provide a novel sequence of active peptides capable of modulating the activity of neutrophil cells identified through the screening of PS-SPCLs. In addition, the present invention provides a pharmaceutical composition that can be applied as a therapeutic agent for neutrophil activity and a disease associated with FPR1 or FPR2 using the active peptide of the novel sequence.

However, the technical problem to be solved by the present invention is not limited to the above-mentioned problems, and other matters not mentioned can be clearly understood by those skilled in the art from the following description.

One aspect of the invention provides a peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 1 to 3. According to one embodiment of the invention, the peptide may be characterized in that it regulates the activity of neutrophil cells, the peptide is characterized in that (a) induces an increase in intracellular calcium ion, (b) cell chemotaxis It may have one or more properties selected from the group consisting of stimulating properties, and (c) properties specifically acting on white blood cells.

In addition, the peptide of SEQ ID NO: 2 or SEQ ID NO: 3 may be characterized by inducing superoxide generation in human neutrophils, the peptide of SEQ ID NO: 1 or SEQ ID NO: 3 acts on the formyl peptide receptor 1 (FPR1) The peptide of SEQ ID NO: 2 may be characterized in that it acts on FPR2 (formyl peptide receptor 2).

Another aspect of the invention provides a pharmaceutical composition comprising a pharmaceutically effective amount of the peptide of claim 1.

The novel peptides according to the present invention promote intracellular calcium ion release through the activation of phospholipase C, a phospholipid hydrolase in neutrophils, and specifically acts on leukocytes. In addition, the mobility of neutrophil cells is promoted by these peptides, which act as chemotactic factors. In addition, it was found that reactive oxygen production, which is an important function of neutrophils, is promoted and acts on FPR1 or FPR2. The present invention is a novel substance capable of regulating the activity of neutrophils, and can be used for the development of therapeutic agents for diseases in which neutrophil activity is important. It is also expected that FPR1 or FPR2 may be applied to the development of therapeutics for diseases related to it.

1 is any one of 19 of intracellular Ca a diagram showing the initial screening results of the PS-SPCLs for screening a peptide that stimulates the ^{2 +} increase, hexapeptide defined in each panel has six positions in human neutrophils cells Defined by one of the L-amino acids (O1 to O6), the remaining five positions consist of a mixture of 19 L-amino acids (excluding cysteine).
Figure 2 shows the results of experiments on the effect of the peptides according to the invention on the increase in Ca ^{2 +} in human neutrophil cells.
3 is a diagram showing the results of experiments with cell specificity of the peptides according to the present invention.
Figure 4 is a view showing the results of experiments chemotaxis of the peptides according to the present invention.
Figure 5 shows the results of measuring the effect on the production of superoxide anion in human neutrophils of the peptides according to the present invention.
Figure 6 is a view showing the results of experiments stimulating the effect of FPR1 or FPR2 of the peptides according to the present invention.

Neutrophil cells play an important role in quickly defending against invading pathogens and other dangerous substances. Thus, we screened hexapeptide combination libraries (PS-SPCLs) comprising more than 47 million different peptide sequences to identify novel hexapeptides that stimulate intracellular calcium ion increase in human neutrophil cells. To develop a substance that can be applied to the development of therapeutic agents for diseases related to cell activity and diseases related to FPR1 or FPR2.

Specifically, the present inventors have synthesized a library of synthetic peptides (47,000,000 sequences) by measuring the release of calcium ions involved in neutrophil activation in order to identify active substances that can regulate the activity of neutrophil cells that play an important role in the innate immune response. ), Whereby the novel peptide active peptide GMMWAI (Gly-Met-Met-Trp-Ala-Ile-CONH ₂ ), MMHWAM (MEt-Met-His-Trp-Ala-Met-CONH ₂ ), And MMHWFM (Met-Met-His-Trp-Phe-Met-CONH ₂ ). The sequence numbers and names of the novel peptides identified are shown in Table 1.

SEQ ID NO: designation order SEQ ID NO: 1 GMMWAI Gly-Met-Met-Trp-Ala-Ile SEQ ID NO: 2 MMHWAM Met-Met-His-Trp-Ala-Met SEQ ID NO: 3 MMHWFM Met-Met- His-Trp-Phe-Met

The peptide has one or more properties selected from the group consisting of (a) induces increased calcium ion in cells, (b) stimulates cellular chemotaxis, and (c) acts specifically on leukocytes. Have

That is, the three peptides promote intracellular calcium ion release through activation of phospholipase C (PLC), a phospholipid hydrolase in neutrophils, and PTX-sensitive G-protein. In addition, the three peptides specifically act on human phagocytes, including neutrophil cells and monocytes, and do not act on non-white blood cells such as fibroblasts or neurons.

The inventors have found that the above three novel peptides that stimulate FIG cell chemotaxis as well as movement in Ca ^{2 +} cell increase throughout the PTX- sensitive G- proteins. Mobility of neutrophil cells was promoted by the three peptides, it can be seen that these peptides act as chemotactic factors.

Neutrophil cells play an important role in the innate immune response by producing large amounts of superoxide anions by extracellular stimuli. Superoxide anions used by human neutrophil cells are well known to kill invading pathogens. Among the peptides MMHWAM, and MMHWFM increased the production of superoxide anion, it can be seen that promotes the production of reactive oxygen, an important function of neutrophils.

In addition, the three peptides act on formyl peptide receptor 1 (FPR1) or formyl peptide receptor 2 (FPR2). FPR binds to G-protein as a receptor for older chemotactic compounds found in phagocytic cells such as neutrophils, monosites, macrophages and dendritic cells. Three types of FPR (FPR, FPR-like FPRL1, and FPRL2) and two types of FPR (FPR1 corresponding to human FPR and FPR2 corresponding to human FPRL1) were identified in humans and mice, respectively. Activation of members of the FPR family induces chemotaxis of leukocytes and induces bactericidal activity through superoxide anion production in neutrophils and monosites. Of these peptides, GMMWAI and MMHWFM act on FPR1 and MMHWAM acts on FPR2.

The present invention provides a pharmaceutical composition comprising a pharmaceutically effective amount of the peptides GMMWAI, MMHWAM, and MMHWFM. The pharmaceutical composition is infection, rheumatoid arthritis, sepsis, ulcerative colitis, prostatitis, osteoporosis, chronic non-infectious pneumonia, transplant rejection, graft versus host disease (GVHD), bronchial asthma, arteriosclerosis, psoriasis, disseminated vascular coagulation It can be used to prevent and treat syndrome (DIC), pneumonia, and acquired respiratory distress syndrome.

Pharmaceutical dosage forms of the compositions of the present invention may be used in the form of their pharmaceutically acceptable salts, and may also be used alone or in combination with other pharmaceutically active compounds as well as in a suitable collection. Salts of the compounds of the present invention are preferably pharmaceutically acceptable salts and are prepared by presently known methods such as adding inorganic bases, organic bases, inorganic acids, organic acids, basic or acidic amino acids to the compounds according to the invention. Can be.

The pharmaceutical composition of the present invention may comprise a pharmaceutically acceptable carrier. The pharmaceutically acceptable carrier may include, but is not limited to, physiological saline, polyethylene glycol, ethanol, vegetable oil, and isopropyl myristate.

The compounds of the present invention may be formulated in ointments or creams for topical application, and may be formulated in conventional saline, water-soluble solvents such as 5% dextrose, or in ratios such as vegetable oils, synthetic fatty acid glycerides, higher fatty acid esters, or propylene glycol. The compounds may be formulated into injections by dissolving, suspending, or emulsifying the compound in an aqueous solvent. Formulations of the present invention may include conventional additives such as solubilizers, isotonic agents, suspending agents, emulsifiers, stabilizers, and preservatives.

In addition, in the present invention, "pharmaceutical effective amount" may be adjusted in various ways depending on the weight, age, sex, health status, diet, administration time, administration method, excretion rate, and severity of the disease of the patient. It is obvious to Preferred dosages of the compounds of the present invention depend on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration, and the duration, but may be appropriately selected by those skilled in the art. Preferably, however, the compound of the present invention is administered at 0.001 to 100 mg / kg body weight per day, more preferably 0.01 to 30 mg / kg body weight. Administration may be administered once a day or may be divided several times. The compounds of the present invention in the pharmaceutical composition should be present in an amount of 0.0001 to 10% by weight, preferably 0.001 to 1% by weight, based on the total weight of the total composition. The pharmaceutical composition of the present invention can be administered to mammals such as mice, mice, livestock, humans, and the like by various routes. The method of administration is not limited and can be administered, for example, orally, rectally, or by intravenous, intramuscular, subcutaneous, intrauterine, or intra-cerebroventricular injection.

Hereinafter, preferred embodiments of the present invention will be described in order to facilitate understanding of the present invention. However, the following examples are provided only for the purpose of easier understanding of the present invention, and the present invention is not limited by the following examples.

[ Example ]

Example  One. Example  Material preparation and method

1-1. material

Peripheral blood mononuclear cells (PBMC) isolation medium (Hictopaque-1077) and cytochrome c were purchased from Sigma (St. Louis, MO). Fura-2pentaacetoxymethylester (fura-2 / AM) was purchased from a molecular probe (Eugene, OR) and PTX was purchased from Calbiocam (San Diego, CA).

1-2. Isolation of leukocytes

Peripheral blood leukocytes were obtained from healthy donors. Human neutrophils were isolated using dextran precipitation, low permeability degradation of erythrocytes and lymphocyte separation media gradient. Peripheral blood mononuclear cells (PBMC) were isolated using a Histopaque-1077 gradient, washed twice with HBSS containing no calcium and magnesium, suspended in RPMI medium containing 10% FBS, and then mononuclear leukocytes were cultured. Incubated at 37 ° C. for 60 minutes to fix on. After the adherent monocytic leukocytes had collected, the cells were washed five times in warm RPMI medium to wash out lymphocytes. This isolated human leukocyte was used immediately.

1-3. Cell culture

NIH Swiss mouse embryo fibroblasts (NIH3T), Rat embryonic fibroblasts (3Y1), preadipocytes (3T3L1), and rat adrenal pheochromocytoma (PC12) cells were obtained from the American type Culture Collection (Rockville, ME) to provide a humidified atmosphere, 5% CO ₂ , The cells were incubated at 95% air and 37 ° C. at about 1 × 10 ⁶ cell numbers.

Example 2. Identification and Properties of Peptides According to the Invention

2-1. Ca in human neutrophil cells ²⁺  Identification of Neutrophil Cell Activating Peptides by Identification of Peptides Stimulating Increase

It was screen both to screening of 114 peptide pools peptides that stimulate Ca ^{2 +} increase (around 47 million peptides) from human neutrophils cells from hexapeptide PS-SPCLs (Positonal Scanning Synthetic Peptide Combinational Library), respectively, from the initial screening the Ca ^{2 +} increase the level of each amino acid is fixed to the induction of the position observed. Specifically, hexapeptide library was obtained from Peptide Library Support Facility of Pohang University of Science and Technology. As a result, 114 peptide pools (Cys were excluded from the composition of the libraries) were dissolved individually in water at a concentration of 27 nM per peptide sequence in each pool. The level of the Grynkiewicz method [Ca ^{2 +]} i was measured using fura-2 / AM for the initial screening of the PS-SPCLs. The prepared cells were incubated at 37 ° C. for 50 minutes with 3 μM fura-2 / AM while continuing stirring in fresh serum-free RPMI 1640 medium. Aliquots to be used for each analysis in the 2 x 10 ⁶ Locke's solution to not have Ca ^{2 +} cells (154 mM NaCl, 5.6 mM KCl , 1.2 mM MgCl 2, 5 mM HEPES, pH 7.3, 10 mM glucose, and 0.2 mM EGTA) Aliquotes were incubated with each pool of peptide pools (50 pM per peptide sequence for initial screening). A corrected fluorescence ratio dual excitation wavelength of 500nm and emission wavelength of the fluorescence change of the measurement at 340nm and 380nm changed in [Ca ^{2 +]} i.

As a result, as shown in FIG. 1, the most active peptide at each position was methionine (M) or glycine (G) at the first position, methionine (M) at the second position, and histidine (3) at the third position. H) or methionine (M), tryptophan (W) in the fourth position, alanine (A) in the multiline position, and methionine (M) or isoleucine (I) in the sixth position.

We synthesized three representative hexapeptides based on the initial screening results of the peptide library. The three hexapeptides are GMMWAI, MMHWAM, and MMHWFM.

2-2. G- proteins and PLC in Mediated Ca ^{2 +}  Inducing increase Peptides

The inventors have measured the stimulation of neutrophil cells, and Ca ^{2 +} concentrations using the above three peptides at various concentrations of 0.01 to 10μM.

As a result, as shown in FIG. 2, the above three peptides have confirmed that the dose-dependently induced by the increase in Ca ^{+ 2.} The highest activity was seen at concentrations of 0.5-5 μM (see FIGS. 2A-2C).

On the other hand, intracellular Ca ^{2 +} increase may be induced by several different routes. Activity of Ca ²⁺ channels as an example leads to the leukocytes increases intracellular Ca ^{2 +.} The present inventors wish to bar hayeotneun sure that the above three peptides increase in Ca ^{2 +} cell levels, which ensure that the relevance of the Ca ^{2 +} channels of the cell surface. Thus, by using some other Ca ^{2 +} channel selective inhibitors of was confirmed whether or not affect intracellular Ca ^{2 +} increase after a pre-culture.

As a result, even using, a human neutrophil cell 1μM nifedifine (voltage-sensitive L type Ca 2 + channel blocker), 10μM diltiazem (voltage-sensitive L type Ca 2 + channel blocker), and 10μM SK & F as shown in 2D If the former culture, derived from MMHWAM intracellular Ca ^{2 +} increase was not affected. This suggests that sikindaneun MMHWAM to increase the Ca ^{2 +} channel dependent path independent of Ca ^{2 +} concentrations in the human neutrophil cells.

The other path of the Ca ^{2 +} cell increase is achieved by the activation of phospholipase seed (Phospholipase C, PLC). In order to examine the role of PLC in the Ca ^{2 +} increase induced by MMHWAM, the PLC inhibitor U-73122 (5μM) or its inactive analogue U-73343 (5μM), ethoxy diphenyl borate to the 2-amino (2- using APB, 5μM), and pre-processing the cells, it was confirmed that younghang on intracellular Ca ^{2 +} increase.

As a result, as shown in Figure 2E, U-73122 was completely inhibited the increase in Ca ^{2 +} derived from MMHWAM. However, U-73343 did not affect. Further, ethoxy diphenyl borate (2-APB) in 2-amino-was also completely inhibited the Ca ^{2 +} increase in human neutrophils derived from MMHWAM cells. This MMHWAM suggests that stimulate Ca ^{2 +} increase by PLC activity in human cells hojung. Thus, MMHWAM was confirmed that not only the presence of extracellular Ca ^{2 +,} even if the member to induce intracellular Ca ^{2 +} increase by the PLC activity.

In addition, the present inventors to confirm the effects of the Ca ^{2 +} increase is derived from the peptide PTX (G _{i / o} G protein inhibitors of type). Therefore, human neutrophil cells were preincubated for 8 hours with 100 ng / ml PTX before stimulation with MMHWAM (5 μM). And, it was compared to those not using the PTX Ca ^{2 +} increase or not.

As a result, as shown in FIG. 2F, the Ca ^{2 +} increase induced from the peptide was almost completely inhibited. This MMHWAM suggests that stimulate Ca ^{2 +} increase by PTX- sensitive G- proteins.

The present inventors were also the other two peptides, and GMMWAI MMHWFM also confirmed that stimulate Ca ²⁺ increase by, Gi protein and a non-PLC Ca ²⁺ channel.

2-3. Remind new Peptide  Leukocyte specificity

The present inventors attempted to determine whether the GMMWAI, MMHWAM and MMHWFM, which stimulate human neutrophil cells, have the same effect on other leukocytes such as monocytes. Thus, stimulating the mononuclear cells using the above three peptides, and the results of measuring the Ca ^{2 +} levels, it was confirmed that it increases the Ca ^{2 +.} In addition, the three peptides were confirmed to have similar concentration dependence as neutrophil cells.

Furthermore, the present inventors have found that the experiment was carried out to determine affect intracellular Ca ^{2 +} increase in outer some white blood cells above three peptides. Stimulate NIH3T3 (NIH Swiss Mouse Embryonic Fibroblasts), 3Y1 (Rat Embryonic Fibroblasts), 3T3L1 (Fat Progenitor Cells), and PC12 (Rat Adrenal Chromocytoma) Cells using the three peptides (5 μM), the Ca ^{2 +} levels were measured.

As a result, as shown in Figure 3, all did not affect the Ca ^{2 +} increase. As a result, the three peptides were confirmed to be specific for human leukocytes.

2-4. New in Human Neutrophil Cells Peptide Chemistry

Since neutrophil cells derived from peptides and chemotaxis are similar to each other, it was examined whether the peptides exhibit chemotactic activity in human neutrophils. Specifically, chemotaxis analysis was performed using a multiwell chamfer (Neuroprobe Inc., Gaithersburg, MD). Briefly, the prepared human neutrophils were suspended in RPMI at 1 × 10 ⁶ cell counts per ml, and 25 μl of suspension was lowered containing peptides by a polyhydrocarbon filter having a pore size of 3 μm. Aliquots were dispensed into the upper wells of the chamber separated from the wells. After culturing at 37 ° C. for 90 min, unmigrated cells were scraped out and cells migrated through a filter were dehydrated, fixed and stained with hematoxylin (Sigma, St. Louis, MO). Five regions were randomly selected at high power field (400 × HPF) to measure the number of stained cells. The results are shown in Fig.

As shown in FIGS. 4A-4C, GMMWAI, MMHWAM, and MMHWFM induced human neutrophil cell mobility within 0.1-5 μM concentration. This suggests that these three peptides induce chemotaxis in human neutrophils.

Various extracellular stimuli, including various chemotactic factors, activate neutrophil cells through PTX-sensitive G-proteins. We sought to ascertain the involvement of PTX-sensitive G-proteins in neutrophil chemotaxis derived from peptides. Human neutrophil cells were preincubated in PTX (1 μg / ml) for 8 hours, and after 5 μM of GMMWAI, MMHWAM, and MMHWFM, respectively, the results of analysis of chemotaxis showed that the chemotaxis of neutrophil cells derived from peptides was completely Inhibited (see FIGS. 4D-4F). As a result, it was confirmed that GMMWAI, MMHWAM, and MMHWFM stimulated neutrophil cell chemotaxis through PTX-sensitive G-protein.

2-5. Of human neutrophil cells Superoxide  Negative ion generation effect

The present inventors measured the effect of the three peptides on the production of superoxide anion in human neutrophils to determine whether reactive oxygen is an important function of neutrophils. Specifically, superoxide anion production was analyzed by measuring cytochrome c reduction using a microtiter 96-well plate ELISA analyzer (Bio-Tek instruments, EL312e, Winooski, VT, USA) (Bae, YS, et al. , Blood 97: 2854, 2001). Human neutrophils (2 × 10 ⁶ cells / RPMI 1640 medium) were incubated with 50 μM of cytochrome c for 5 min at 37 ° C. and then incubated with each peptide. Superoxide production was measured for change in absorbance at 550 nm for 5 minutes at 1 minute intervals. The results are shown in Fig.

As shown in FIG. 5A, various concentrations of GMMWAI failed to produce superoxide anions. However, as shown in FIGS. 5B and 5C, the other two novel peptides (MMHWAM, MMHWFM) have greatly increased superoxide anion production.

2-6. FPR1  or FPR2 Irritant effect

Formyl peptide receptors are representative chemotactic receptors in human neutrophils. The present inventors tried to determine whether the three peptides act on FPR1 and its associated receptor. FPR1 antagonists (CsH) and FPR2 antagonists (WRW ⁴ ) were used for this purpose.

As a result, the Figure 6A and, as shown in Figure 6C, GMMWAI (5μM) and MMHWFM (5μM) to induce a Ca ^{2 +} increase is been completely inhibited by CsH (10μM), it is not inhibited by WRW ⁴ (10μM) Did. However,, MMHWAM (5μM), which induce increase in Ca ^{2 +,} as shown in Figure 6B was completely inhibited by the non-CsH ⁴ WRW. As a result, it was confirmed that GMMWAI and MMHWFM acted on FPR1, and MMHWAM acted on FPR2.

On the other hand, the inventors also used the vector, FPR1-, or FPR2-expressing RBL-2H3 cells to confirm the action on FPR1 or FPR2.

As a result, as shown in FIG 6E, using the GMMWAI (5μM) and MMHWFM (5μM) when the stimulating FPR1- expressing RBL-2H3 cells, the cells were increased in Ca ^{2 +} is significant. In addition, as shown in FIG. 6D and FIG. 6F, Vector -, or FPR2- expression is increased in Ca ^{2 +} cells were not induced in the RBL-2H3 cells.

On the other hand, MMHWAM (5μM) is FPR1- expressing RBL-2H3 cells, the cells are intracellular Ca ²⁺ it did not increase the induced, intracellular Ca ²⁺ increase in FPR2- cells expressing RBL-2H3 cells were observed.

Thus, it was confirmed once again that GMMWAI and MMHWFM acted on FPR1, not FPR2, and MMHWAM acted on FPR2.

The foregoing description of the present invention is intended for illustration, and it will be understood by those skilled in the art that the present invention may be easily modified in other specific forms without changing the technical spirit or essential features of the present invention. will be. It is therefore to be understood that the above-described embodiments are illustrative in all aspects and not restrictive.

<110> SUNGKYUNKWAN UNIVERSITY Foundation for Corporate Collaboration <120> Novel peptides that stimulate human neutrophils <130> PB11-09872 <160> 3 <170> Kopatentin 2.0 <210> 1 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> GMMWAI <400> 1 Gly Met Met Trp Ala Ile   1 5 <210> 2 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> MMHWAM <400> 2 Met Met His Trp Ala Met   1 5 <210> 3 <211> 6 <212> PRT <213> Artificial Sequence <220> <223> MMHWFM <400> 3 Met Met His Trp Phe Met   1 5

Claims (7)

Peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NO: 1 to 3.
The method of claim 1,
The peptide is characterized in that to regulate the activity of neutrophil cells.
The method of claim 1,
The peptide has one or more properties selected from the group consisting of (a) induces increased calcium ion in cells, (b) stimulates cellular chemotaxis, and (c) acts specifically on leukocytes. Peptide having.
The method of claim 1,
The peptide of SEQ ID NO: 2 or SEQ ID NO: 3, characterized in that to induce superoxide production in human neutrophils.
The method of claim 1,
The peptide of SEQ ID NO: 1 or SEQ ID NO: 3, characterized in that acting on FPR1 (formyl peptide receptor 1).
The method of claim 1,
The peptide of SEQ ID NO: 2 is characterized in that it acts on FPR2 (formyl peptide receptor 2).
A pharmaceutical composition comprising a pharmaceutically effective amount of the peptide of claim 1.

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