Human neutrophil adherence to thrombospondin occurs through a CD11/CD18- independent mechanism

• Published in: The Journal of immunology (1950) Vol. 146; no. 11; pp. 3945 - 3952
• Main Authors: Suchard, SJ, Burton, MJ, Dixit, VM, Boxer, LA
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Assoc Immnol 01-06-1991; American Association of Immunologists
• Subjects: Analysis of the immune response. Humoral and cellular immunity; Antigens, CD - physiology; Biological and medical sciences; CD11 Antigens; CD18 Antigens; Cell Adhesion; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunobiology; Neutrophils - physiology; Oligopeptides - physiology; Organs and cells involved in the immune response; Peptide Fragments - physiology; Platelet Membrane Glycoproteins - physiology; Thrombospondins; Human; Neutrophile; Granulocyte; Molecular interaction; Extracellular matrix; Glycoproteins; Kinetics; Adhesion; Mechanism; Thrombospondin
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.146.11.3945

Thrombospondin (TSP), a 450-kDa trimeric glycoprotein secreted by platelets and endothelial cells at sites of tissue injury or inflammation, may play an important role in polymorphonuclear leukocyte (PMN) adherence to blood vessel walls before diapedesis. We have examined the adherence of PMN to TSP and compared it to adherence to other extracellular matrix proteins. PMN adherence to TSP-coated plastic was complete by 60 min with spreading completed by 2 h. The kinetics of adhesion and spreading on TSP were similar to that of vitronectin (VN), laminin (LN), and fibronectin (FN). Activation of PMN with the calcium ionophore A23187 or the chemotactic peptide FMLP increased PMN adherence to LN and FN, but not to TSP or VN, suggesting that PMN activation may differentially regulate expression of TSP and VN receptors as compared to LN and FN receptors. The specificity of PMN adherence to TSP was confirmed by competition with saturating amounts of TSP and inhibition with anti-TSP antibodies. mAb A6.1, which binds to the protease-resistant core of TSP, was the most effective in blocking PMN adherence to TSP. Using TSP proteolytic fragments, we demonstrated that the primary interaction of PMN with TSP was mediated through the 140-kDa COOH-terminal domain. Inasmuch as the 140-kDa fragment of TSP contains an Arg-Gly-Asp sequence similar to the cell recognition site of FN and VN, we determined whether RGDS peptides would inhibit PMN adhesion. RGDS did not significantly inhibit PMN adhesion to TSP, VN, or LN, but reduced PMN adhesion to FN by 50%. To determine if PMN adhesion to TSP was mediated by a beta 2 integrin receptor such as LFA-1, MO-1, or p150,95, we performed adhesion assays using PMN isolated from patients with leukocyte adhesion deficiency that lack beta 2 receptors. Leukocyte adhesion deficiency PMN exhibited normal adherence to TSP. In contrast, adherence to VN, LN, and FN was reduced by 95%. Therefore, adherence to TSP is probably not mediated by a beta 2 integrin receptor. These data contribute to the accumulating evidence that PMN can interact with extracellular matrix proteins through a CD11/CD18-independent process.