Leukocyte complement receptors and adhesion proteins in the inflammatory response: insights from an experiment of nature.
The complement receptor type 3 (CR3) mediates phagocytosis and degradation of iC3b-opsonized particles by macrophages and granulocytes. The CR3 is identical to the Mac-1 molecule, which is composed of two non-covalently associated glycoprotein subunits, alpha M of Mr 170,000 and beta of Mr 95,000. Patients with recurring, life-threatening bacterial infections have been identified who have moderate (95%) or severe (greater than 99%) deficiency of Mac-1 and of the related LFA-1 and p150,95 molecules. The primary defect is in the shared beta subunit of these molecules. Patient leukocytes are not only deficient in CR3 but in a wide variety of adhesion-dependent functions, including granulocyte chemotaxis, adherence to surfaces, and aggregation. Monoclonal antibodies to the Mac-1 alpha subunit and to the beta subunit block these functions. The hypothesis will be advanced that Mac-1 functions dually as the CR3 and in 'nonspecific' adherence reactions. Adherence functions are stimulated in normal granulocytes by chemoattractants, which also induce a rapid 5-fold increase in Mac-1 and p150,95 on the cell surface. It is proposed that absence of Mac-1 and p150,95 expression and upregulation by patient granulocytes is causally related to their inability to extravasate and migrate into inflammatory sites.
D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology; D000954:Antigens, Surface / Q000276:immunology*; D002448:Cell Adhesion; D002634:Chemotaxis, Leukocyte; D006098:Granulocytes / Q000502:physiology; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000276:immunology; D007249:Inflammation / Q000276:immunology*; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D011951:Receptors, Complement / Q000502:physiology*; D017463:Receptors, Complement 3b
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D011951:Receptors, Complement; D017463:Receptors, Complement 3b