Selective adhesion of macrophages to denatured forms of type I collagen is mediated by scavenger receptors.
Macrophages (M&phi;s) are multifunctional immune cells which are involved in the regulation of immune and inflammatory responses, as well as in tissue repair and remodeling. In tissues, M&phi;s reside in areas which are rich in extracellular matrix (ECM), the structural component which also plays an essential role in regulating a variety of cellular functions. A major ECM protein encountered by M&phi;s is type I collagen, the most abundant of the fibril-forming collagens. In this study, the adhesion of RAW 264.7 murine Mphis to native fibrillar, monomeric, and denatured type I collagen was investigated. Using atomic force microscopy, structural differences between fibrillar and monomeric type I collagen were clearly resolved. When cultured on fibrillar type I collagen, Mphis adhered poorly. In contrast, they adhered significantly to monomeric, heat-denatured, or collagenase-modified type I collagen. Studies utilizing anti-beta1 and -beta2 integrin adhesion-blocking antibodies, RGD-containing peptides, or divalent cation-free conditions did not inhibit Mphi; adhesion to monomeric or denatured type I collagen. However, macrophage scavenger receptor (MSR) ligands and anti-MSR antibodies significantly blocked Mphi; adhesion to denatured and monomeric type I collagen strongly suggesting the involvement of the MSR as an adhesion molecule for denatured type I collagen. Further analysis by Western blot identified the MSR as the primary receptor for denatured type I collagen among Mphi; proteins purified from a heat-denatured type I collagen affinity column. These findings indicate that Mphis adhere selectively to denatured forms of type I collagen, but not the native fibrillar conformation, via their scavenger receptors.
Gowen
B B
BB
Department of Microbiology and Immunology, University of South Carolina, School of Medicine, Columbia 29208, USA.
Borg
T K
TK
Ghaffar
A
A
Mayer
E P
EP
D000818:Animals; D018821:CD18 Antigens / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D003094:Collagen / Q000378:metabolism*; D006361:Heating; D008024:Ligands; D008264:Macrophages / Q000502:physiology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D011489:Protein Denaturation; D011971:Receptors, Immunologic / Q000378:metabolism*; D051116:Receptors, Scavenger; D014407:Tumor Cells, Cultured
D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D008024:Ligands; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D003094:Collagen