KR960700071A - METHOD FOR MODULATING TRANSENDOTHELIAL MIGRATION OF CELLS PROMOTING INFLAMMATION, AND RELATED METHODS OF MEASUREMENT THEREOF - Google Patents

Abstract

Rapid transport or chronic inflammatory leukocytes and other endothelial cell migration of other cells can be inhibited by the administration of anti-PECAM-1 reagents. In particular, endothelial cell migration is caused by the activity of platelet endothelial cell adhesion molecules (PECAM), as inhibition of Neutrophil and mononuclear leukocyte TEM occurs in the face of recombinant soluble PECAM or large PECAM antibodies that are cells derived from single cells. It seems to be adjusted. Disclosed is a method of regulating endothelial cell layer migration and corresponding agents as it relates to diagnostics and drug discovery assays. Inhibition of such endothelial cell migration will serve to prevent and / or reduce organ damage due to inflammation, and the methods of the present invention may be particularly useful for the treatment of acute inflammation as well as for chronic inflammation.

Description

METHOD FOR MODULATING TRANSENDOTHELIAL MIGRATION OF CELLS PROMOTING INFLAMMATION, AND RELATED METHODS OF MEASUREMENT THEREOF

As this is a public information case, the full text was not included.

Claims (46)

Infectious or non-infectious mammals consisting of administering an amount of a TEM regulatory agent selected from the group consisting of antibodies to PECAM, a fit of PECAM activity, recombinant human PECAM-1 (rhPECAM-1), and active fragments thereof A method for regulating endothelial cell transmembrane migration (TEM) of leukocytes into acute and / or chronic inflammatory lesions of a patient. The method of claim 1, wherein the anti-PECAM antibody is anti-PECAM-1. The method of claim 1, wherein the anti-PECAM antibody is antibody hec7, or an active fragment thereof, made from cells derived from a single cell. 4. The method of claim 3, wherein the antibody, or active fragment thereof, made in a cell derived from a single cell regulates endothelial cell transmembrane migration of leukocytes to an inflammatory lesion, which is prepared from hybridoma Hec7.2, ATCC assay No. HB11227. How to. The method of claim 1, wherein the endothelial transmembrane migration of leukocytes is associated with anterior lobe. The method of claim 1, wherein the endothelial transcellular translocation of leukocytes is associated with trauma of non-infectious disease. The method of claim 1, wherein the endothelial cell transmembrane migration of leukocytes is associated with endotoxin shock. The method of claim 1, wherein the endothelial transcellular transmembrane migration of leukocytes is associated with respiratory distress syndrome in an adult. The endothelium of leukocytes into inflammatory lesions according to claim 1, wherein the endothelial transcellular translocation of leukocytes is associated with a disease state selected from the group consisting of meningitis, encephalitis, arthritis, uveitis, colitis, dermatitis, and respiratory distress syndrome in adults. A method of controlling cell transmembrane migration. The method of claim 1, wherein the endothelial transcellular translocation of leukocytes comprises organ transplantation or taga transplantation; Atherosclerosis; Pernicious anemia, complex sclerosis, progressive lupus erythema, rheumatoid arthritis, Sjogren's syndrome, progressive systemic sclerosis (sclerosis), interstitial spondylitis, polymyositis, dermatitis, pemphigus, pampioid, type I diabetes mellitus, Muscular dysfunction, Hashimoto's thyroiditis, Graves' disease, Goodpacher's disease, mixed-related tissue disease, sclerotic cholecystitis, inflammatory bowel disease including Crohn's disease (local enteritis) and ulcerative colitis, pernicious anemia, inflammatory skin disease ; Common intervening pneumonia, asbestos deposition, silicosis, beryliosis, talcosis, all forms of pneumoconiosis, similar sarcoma (of the lungs and other organs), exfoliative intervening pneumonia, lymphoid pneumonia, large cell interstitial pneumonia , Interstitial pneumonia of cells, exogenous allergy Malveolitis, granulomatosis of Bengener and related forms of angularity; Arteritis; Temporal arteritis and polyarteritis; Inflammatory dermatitis, in which autoimmunity is not presumed; Chronic active hepatitis; Delayed-type hypersensitivity reactions (eg lacquer dermatitis); Pneumonia or other respiratory tract salts due to any cause; Etiological adult respiratory distress syndrome (ARDS); Lightning, inflammatory edema; Immediate hypersensitivity reactions including but not limited to asthma, hay fever, skin allergies, acute hypersensitivity; Arteritides, including but not limited to temporal arteritis and polyarteritis nodosa; Of acute and / or chronic Gromerulonepritis due to etiology, including diseases involving sensitive deployment of immune complexes, rheumatic fever, especially post-infectious Gromerulonepritis, systemic ulcers Acute exacerbation; Pielonapritis; Cellulitis; Cystitis; Acute cholecystitis; And endothelial cell transmembrane migration of leukocytes to the inflammatory lesion, which is derived from a state selected from the group consisting of sequelae of a state producing transient ischemia. The method of claim 1, wherein the endothelial transmembrane migration of the leukocytes to the inflammatory lesion is inhibited for the treatment of inflammation and a condition associated with it. The method of claim 1, wherein the endothelial cell transmembrane migration of the leukocytes to the inflammatory lesions is enhanced to improve the immune treated state of the mammal. The method of claim 1, wherein the endothelial transmembrane migration of leukocytes results from a treatment resulting from treatment. Consisting of administering to a patient in need of such treatment a therapeutic amount of an agent selected from the group consisting of an antibody against PECAM, an appropriate number of PECAM activity, recombinant human PECAM-1 (rhPECAM-1), and active fragments thereof. A method of treating inflammation in tissues and organs of a patient caused by a condition of transmission or non-infection. The method of claim 14, wherein the anti-PECAM antibody is anti PECAM-1. The method of claim 14, wherein the anti-PECAM antibody is antibody hec7, or an active fragment thereof, made from cells derived from a single cell. The method of claim 16, wherein the antibody, or active fragment thereof, made in a cell derived from a single cell is prepared from hybridoma hec7.2, ATCC assay No.HB11227. The method of claim 14, wherein the agent is administered intravenously. The method of claim 14, wherein the agent is administered orally. The method of claim 14, wherein the agent is administered parenterally. The method of claim 14, wherein the inflammation is associated with transmission. The method of claim 14, wherein the inflammation is associated with non-contagious trauma. The method of claim 14, wherein the inflammation is associated with endotoxin shock. The method of claim 21, wherein the infection is associated with a disease selected from the group consisting of meningitis, encephalitis, arthritis, uveitis, colitis, and respiratory distress syndrome in adults. The method of claim 14, wherein the inflammation is organ transplantation or taga transplantation; Atherosclerosis; Pernicious anemia, complex sclerosis, progressive lupus erythema, rheumatoid arthritis, Sjogren's syndrome, progressive systemic sclerosis (sclerosis), interstitial spondylitis, polymyositis, dermatitis, pemphigus, pampioid, type I diabetes mellitus, Muscular dysfunction, thyroiditis of Hashimodo, Graves' disease, Goodpacher's disease, mixed-related tissue disease, sclerotic cholecystitis, inflammatory visceral diseases including Crohn's disease (local enteritis) and ulcerative colitis, pernicious anemia, inflammatory skin disease; Common intervening pneumonia, asbestos deposition, silicosis, beryliosis, talcosis, all forms of pneumoconiosis, similar sarcoma (of the lungs and other organs), exfoliative intervening pneumonia, lymphoid pneumonia, large cell interstitial pneumonia , Interstitial pneumonia of cells, exogenous allergy Malveolitis, granulomatosis of Bengener and related forms of angularity; Arteritis; Temporal arteritis and polyarteritis; Inflammatory dermatitis, in which autoimmunity is not presumed; Chronic active hepatitis; Delayed-type hypersensitivity reactions (eg lacquer dermatitis); Pneumonia or other respiratory tract salts due to any cause; Etiological adult respiratory distress syndrome (ARDS); Lightning, inflammatory edema; Immediate hypersensitivity reactions including but not limited to asthma, hay fever, skin allergies, acute hypersensitivity; Arteritides, including but not limited to temporal arteritis and polyarteritis nodosa; Of acute and / or chronic Gromerulonepritis due to etiology, including diseases involving sensitive deployment of immune complexes, rheumatic fever, especially post-infectious Gromerulonepritis, systemic ulcers Acute exacerbation; Pielonapritis; Cellulitis; Cystitis; Acute cholecystitis; And a method selected from the group consisting of sequelae of a condition producing transient ischemia. The method of claim 14, wherein the inflammation of tissues and organs of the patient is treated. The method of claim 26, wherein the anti-PECAM antibody is anti-PECAM-1. 27. The method of claim 26, wherein the anti-PECAM antibody is antibody hec7, or an active fragment thereof, made from a cell derived from a single cell. 27. The method of claim 26, wherein the anti-infective agent is a betalactam antibiotic. 27. The method of claim 26, wherein the agent is administered intravenously. The method of claim 26, wherein the agent is administered orally. 27. The method of claim 26, wherein the inflammation is associated with endotoxin shock. The method of claim 26, wherein the inflammation is associated with respiratory distress syndrome in an adult of cause of transmission. 27. The method of claim 26, wherein the infection is associated with a disease selected from the group consisting of meningitis, encephalitis, arthritis, uveitis, colitis, and respiratory distress syndrome in adults. 27. The method of claim 26, wherein the inflammation is organ transplantation or taga transplantation; Pernicious anemia, complex sclerosis, progressive lupus erythema, rheumatoid arthritis, Sjogren's syndrome, progressive systemic sclerosis (sclerosis), interstitial spondylitis, polymyositis, dermatitis, pemphigus, pampioid, type I diabetes mellitus, Muscular dysfunction, thyroiditis of Hashimodo, Graves' disease, Goodfacher's disease, mixed-related tissue disease, sclerotic cholecystitis, inflammatory visceral diseases including Crohn's disease (local enteritis) and ulcerative colitis, pernicious anemia, inflammatory skin disease; Common intervening pneumonia, asbestos deposition, silicosis, beryliosis, talcosis, all forms of pneumoconiosis, similar sarcoma (of the lungs and other organs), exfoliative intervening pneumonia, lymphoid pneumonia, large cell interstitial pneumonia , Interstitial pneumonia of cells, exogenous allergy Malveolitis, granulomatosis of Bengener and related forms of angularity; Arteritis; Temporal arteritis and polyarteritis; Inflammatory dermatitis, in which autoimmunity is not presumed; Chronic active hepatitis; Delayed-type hypersensitivity reactions (eg lacquer dermatitis); Pneumonia or other respiratory tract salts due to any cause; Etiological adult respiratory distress syndrome (ARDS); Lightning, inflammatory edema; Immediate hypersensitivity reactions including but not limited to asthma, hay fever, skin allergies, acute hypersensitivity; Arteritides, including but not limited to temporal arteritis and polyarteritis nodosa; Of acute and / or chronic Gromerulonepritis due to etiology, including diseases involving sensitive deployment of immune complexes, rheumatic fever, especially post-infectious Gromerulonepritis, systemic ulcers Acute exacerbation; Pielonapritis; Cellulitis; Cystitis; Acute cholecystitis; And a method selected from the group consisting of sequelae of a condition producing transient ischemia. A method for measuring endothelial cell transmembrane migration of leukocytes, comprising: A. preparing a test substrate from a colony of human endothelial cell cells; Obtaining a sample of a biological agent believed to contain a large amount of said white blood cells in a mammal; Incubating the biological drug sample of step B with the test substrate for a time sufficient for the white blood cell to regenerate; And D. Testing the culture of step C by examining the location and number of said leukocytes that adhere to the negative between cells of said test substrate. Endothelial cell migration in mammals. And a method of measuring the role of PECAM therein, comprising: A. preparing a test substrate from a population of human endothelial cell layers; B. Obtaining a feed of a biological agent from said mammal containing leukocytes; Incubating purified water of the biological drug sample of step B with said test substrate for a time sufficient for said white blood cells to regenerate; The test substrate and an agent capable of controlling endothelial cell migration of leukocytes are prepared by further incubating purified water of the biological drug sample of step B for the same time as step C, wherein the agent is an antibody against PECAM, PECAM Equation of activity, recombinant human PECAM-1 (rhPECAM-1), agonists of PECAM activity, and active fragments thereof; E. Measuring the PECAM function in terms of endothelial cell migration of the white blood cells by testing the culture of step C and comparing the results to the culture of step D. A method of discovering and circulating a modulator of mammalian PECAM function, comprising: A. preparing a test substrate from a colony of human endothelial cell cells, and B. a group consisting of plasma, serum, and other body fluids from the mammal Obtaining a biological drug sample selected from; C. Prepare at least one test latency by culturing a large number of leukocytes from the same mammal or another mammal without PECAM fusion for a time sufficient to transfect the leukocytes with or without purified water from step B and with the test substrate and ; D. At least one control standard by further culturing purified water of leukocytes from a test mammal or a separate mammal with or without an agent capable of regulating the life of leukocytes and with or without the agent for the same time as step C. Wherein the agent is selected from the group consisting of antibodies to PECAM, recombinant PECAM-1 (rhPECAM-1) for PECAM, agonists of PECAM activity, and their active fragments; And E. The cultures of steps C and D are converted to endothelial cell layer migration of the leukocytes by comparison between the test, step test latency rivers, and step D control standard, and comparing the test latency to the control standard. Measuring PECAM function. The mammalian PECAM function of claim 37 or 38, wherein the biological drug sample is selected from a mammal in which inflammation is believed to develop, is suspected of developing or is in progress, and is suspected of altering the PECAM function. How to find and circulate a modulator of. 39. The method of claim 37 or 38, wherein the time of incubation of steps C and D is a period of time sufficient to result in endothelial cell migration of leukocytes without a PECAM agonist, wherein the method comprises the discovery and / or presence of the PECAM agonist Or circulating to discover a modulator of mammalian PECAM function that extends to measurement. The method of claim 37 or 38, wherein the control standard comprises a biological agent selected from a normal mammal arranged as an agent of step D, a biological agent selected from a normal mammal cultured with an agent of step D, and an agent of step D and And / or circulating to discover modulators of mammalian PECAM function, provided that the method without agent is prepared by performing the method with a material selected from the group consisting of leukocytes normalized to known changes. 39. The biological liquid sample according to claim 37 or 38, wherein the biological drug sample selected from the mammal under test is a biological liquid sample selected from a biological liquid sample selected from a biological drug sample containing non-normal leukocytes known to be abnormal in mammals and PECAM function. Wherein the control standard of step D is prepared with an activator of PECAM cultured with known inhibitors and / or normal leukocytes. The method of claim 37 or 38, wherein the biological agent sample is selected from a mammal in a condition known to cause inflammation and / or inflammation, and the method is performed on a regular and regular basis so that the inflammation and And / or circulate to discover a modulator of mammalian PECAM function that is intended to monitor any changes in PECAM function during progression and prevalence of the condition. 39. The method of claim 37 or 38, wherein said method contains a method for assessing the likelihood of inflammation and / or prolonged endothelial cell migration. 39. The method of claim 37 or 38, wherein in step C, the biological drug sample is incubated not only with the test substrate but also with a drug or agent or agent that is believed to be capable of controlling endothelial cell migration. A method for circulating and discovering a modulator of PECAM function in a mammal, comprising assaying to filter the drug or agent for determination of and / or determination of the efficacy in the treatment of a particular patient. The combination of the biological agent sample and the test substrate according to claim 37 or 38 for monitoring the potency of the agent and / or agents known to affect the endothelial cell layer migration in different states. And / or circulating to discover a modulator of mammalian PECAM function, further comprising culturing a therapeutic agent. ※ Note: The disclosure is based on the initial application.