We have previously reported that COMP (cartilage oligomeric matrix protein) is prominent in cartilage but is also present in tendon and binds to collagens I and II with high affinity. Here we show that COMP influences the fibril formation of these collagens. Fibril formation in the presence of pentameric COMP was much faster, and the amount of collagen in fibrillar form was markedly increased. Monomeric COMP, lacking the N-terminal coiled-coil linker domain, decelerated fibrillogenesis. The data show that stimulation of collagen fibrillogenesis depends on the pentameric nature of COMP and not only on collagen binding. COMP interacts primarily with free collagen I and II molecules, bringing several molecules to close proximity, apparently promoting further assembly. These assemblies further join in discrete steps to a narrow distribution of completed fibril diameters of 149 ؎ 16 nm with a banding pattern of 67 nm. COMP is not found associated with the mature fibril and dissociates from the collagen molecules or their early assemblies. However, a few COMP molecules are found bound to more loosely associated molecules at the tip/end of the growing fibril. Thus, COMP appears to catalyze the fibril formation by promoting early association of collagen molecules leading to increased rate of fibrillogenesis and more distinct organization of the fibrils.

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The high turnover of COMP in SSc skin suggests a pathophysiological role. Serum COMP shows promise as a new biomarker in SSc.

Collagen XVI is integrated tissue-dependently into distinct fibrillar aggregates, such as D-banded cartilage fibrils and fibrillin-1-containing microfibrils. In skin, the distribution of collagen XVI overlaps that of the collagen-binding integrins ␣1␤1 and ␣2␤1. Basal layer keratinocytes express integrin ␣2␤1, whereas integrin ␣1␤1 occurs in smooth muscle cells surrounding blood vessels, in hair follicles, and on adipocytes. Cells bearing the integrins ␣1␤1 and ␣2␤1 attach and spread on recombinant collagen XVI. Furthermore, collagen XVI induces the recruitment of these integrins into focal adhesion plaques, a principal step in integrin signaling. Of potential physiological relevance, these integrin-collagen XVI interactions may connect cells with specialized fibrils, thus contributing to the organization of fibrillar and cellular components within connective tissues. In cell-free binding assays, collagen XVI is more avidly bound by ␣1␤1 integrin than by ␣2␤1 integrin. Both integrins interact with collagen XVI via the A domain of their ␣ subunits. A tryptic collagen XVI fragment comprising the collagenous domains 1-3 is recognized by ␣1␤1 integrin. Electron microscopy of complexes of ␣1␤1 integrin with this tryptic collagen XVI fragment or with full-length collagen XVI revealed a unique ␣1␤1 integrin-binding site within collagen XVI located close to its C-terminal end.Collagen XVI belongs to the fibril-associated collagens with interrupted triple helices (FACIT) 3 family of collagens (1, 2) and is composed of 10 collagenous domains, designated as COL1-10, which are flanked by 11 noncollagenous (NC) regions (3). It constitutes a minor component of the extracellular matrices (ECM) of skin and cartilage. Despite its integration into small heterotypic D-banded fibrils of cartilage, collagen XVI is not generally a component of D-banded fibrils, which contain several types of collagens and further constituents, i.e. small leucine-rich proteoglycans and noncollagenous glycoproteins, in an alloy-like mixture (4, 5). In a tissue-specific manner, collagen XVI is incorporated into structurally and functionally discrete matrix aggregates, such as in specialized fibrillin-1-rich microfibrils in skin. Collagen XVI preferentially associates with that part of the microfibrillar apparatus lacking an amorphous elastin core and is localized in the dermal epidermal junction (DEJ) zone of the papillary dermis (4). Here the microfibrils insert perpendicularly into the basement membrane. This location suggests that collagen XVI plays an active role in anchoring microfibrils to basement membranes. Despite its occurrence in the dermis, it is not only produced by fibroblasts but also by keratinocytes, similarly to type VII collagen (6, 7). However, the mechanism by which these collagens are transported across the basement membrane and incorporated into the mesenchymal stroma is yet unknown. Although many matrix proteins self-assemble and thus contribute to the organization of supramolecular networks, cells also affect the architecture ...

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Species of pathogenic staphylococci and streptococci express several cell wall-bound or released proteins that specifically interact with host components involved in e.g. the blood clotting and the complement system or with extracellular matrix (ECM) 3 proteins (1, 2). Streptococcus equi subspecies equi and subspecies zooepidemicus are both important horse pathogenic bacteria (3). Subspecies equi causes the serious horse respiratory disease called strangles. Subspecies zooepidemicus is considered as an opportunistic commensal, often occurring in the upper respiratory tract of horses. In subspecies zooepidemicus, two cell wall-anchored fibronectin (FN)-binding proteins have been identified, FNZ (4) and FNZ2 (5). In subspecies equi the analogues of these proteins are denoted FNE (6) and FNEB (7), respectively. The different FN-binding proteins expressed by both subspecies display distinct binding specificities and affinities to FN (7). A major difference between FNE and FNZ is that a frameshift mutation in the fne gene results in a truncated protein that is secreted to the growth medium, i.e. FNE. We have previously shown that a recombinant protein representing the N-terminal half of FNZ, denoted FNZN, binds both FN and native collagen type I and in addition, stimulates collagen gel contraction (8).Loose interstitial connective tissues surround all peripheral blood vessels that are involved in the exchange of solutes from plasma to tissues (for a review see Ref. 9). Connective tissue cells participate actively in the fluid balance by controlling the IFP that is normally around zero but lowered during anaphylactic and inflammatory reactions (10). A reduction in IFP provides a driving force for edema formation during inflammation and burn injuries. Edema formation is one of the classical signs of inflammation induced by e.g. tissue reactions to invading bacteria. The pathophysiological relevance of edema formation is most likely to increase drainage from the tissue, as well as to facilitate for phagocytes and soluble antimicrobial proteins to reach the infectious foci.Data from our laboratories suggest that control of IFP and edema formation depends on integrins (10). The collagenbinding integrin ␣2␤1 maintains IFP during homeostasis in rat dermis (11). A lowered dermal IFP resulting from anaphylaxis or blockade of collagen-binding ␤1 integrins can be normalized * This study was supported in part by grants from the Swedish Cancer Foundation (to K. R.), the Swedish Research Council (to K. R. and D. H.), the Gustaf V:s 80-årsfond (to K. R. and D. H.), the Research Council of Norway (to R. K. R.), the AgriFunGen program at the Swedish University of Agricultural Sciences (to B. G.), the Swedish Horse Board (SSH:0447057) (to B. G.), and the Anna-Greta Crafoord Foundation (to A. K.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 3 The abbrevia...

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