Adhesomes: specific granules containing receptors for laminin, C3bi/fibrinogen, fibronectin, and vitronectin in human polymorphonuclear leukocytes and monocytes.

Abstract

Abstract. We have localized several major extracellular matrix protein receptors in the specific granules of human polymorphonuclear (PMN) and monocytic leukocytes using double label immunoelectron microscopy (IEM) with ultrathin frozen sections and colloidal-gold conjugates. Rabbit antibodies to 67-kD human laminin receptor (LNR) were located on the inner surface of the specific granule membrane and within its internal matrix. LNR antigens co-distributed with lactoferrin, a marker of specific granules, but did not co-localize with elastase in azurophilic granules of PMNs. Further, CDllb/CD18 (leukocyte receptor for C3bi, fibrinogen, endothelial cells, and endotoxin), mammalian fibronectin receptor (FNR), and vitronectin receptor (VNR) antigens were also co-localized with LNR in PMN specific granules. A similar type of granule was found in monocytes which stained for LNR, FNR, VNR, CDI8, and lysozyme. Activation of PMNs with either PMA, f-met-leu-phe (fMLP), tumor necrosis factor (TNF), or monocytic leukocytes with lipopolysaccharide (LPS), induced fusion of specific granules with the cell membrane and expression of both LNR and CD18 antigens on the outer cell surface. Further, stimulation led to augmented PMN adhesion on LN substrata, and six-to eightfold increases in specific binding of soluble LN that was inhibited by LNR antibody. These results indicate that four types of extracellular matrix receptors are located in leukocyte specific granules, and suggest that upregulation of these receptors during inflammation may mediate leukocyte adhesion and extravasation. We have thus termed leukocyte specific granules adhesomes.XTRAVASATION of polymorphonuclear leukocytes (PMNs) m and monocytes and their entrance into inflammatory tissue sites requires that they adhere to and penetrate the capillary endothelium, the basement membrane, and the stromal connective tissue (14,42,60). The hematogenous spread of metastatic cells occurs via a similar mechanism (3, 32). Certain cell surface receptors for extracellular l igands play central roles in these adhesion-dependent processes, and the molecular mechanisms underlying these interactions are being elucidated (27,36,48,49).The dominant adhesive ligand of basement membranes is laminin (LN) (36), whereas fibronectin (FN) and vitronectin (VN) are attachment ligands of the connective tissue stroma (23,48,49); other important adhesive molecules such as ICAM-1 and ELAM-1 are expressed on the endothelial cell surface (8,9,13,35). Several types of laminin receptors (LNRs) have been described. A LNR with a molecular mass of 67 kD has been identified in neoplastic cells, PMNs, mac-1. Abbreviations used in this paper: ECMR, extracellular matrix receptor; fMLP, f-met-leu-phe; FN, fibronectin; FNR, fibronectin receptor; IEM, immunoeleetron microscopy; LN, laminin; LNR, laminin receptor; LPS, lipopolysaccharide; PMN, polymorphonuclear; TNF, tumor necrosis factor; VN, vitronectin; VNR, vitronectin receptor. rophages, and myocytes (25,31,37,46,60,61,68,78). This receptor consists of a si...

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