Collagen‐Bound α₁‐Microglobulin in Normal and Healed Tissues and its Effect on Immunocompetent Cells

Abstract

The mechanisms devoted to the protection of the extracellular matrix collagen from the inflammatory insult are not fully understood. We investigated the presence of the immunosuppressive glycoprotein alpha1-microglobulin in healed tissues such as scars and periprosthetic membranes, comparing them with normal skin. Immunohistochemistry showed that alpha1-microglobulin was mainly present along collagen fibrils and in the epidermis. The presence of this protein was confirmed by Western blot of the tissue homogenates, while ELISA showed lower levels in the healed tissues. In vitro, the purified alpha1-microglobulin bound collagen by a cooperative mechanism and attenuated the collagen-induced activation of the mononuclear cells.

A1M, an extravascular tissue cleaning and housekeeping protein

“…It is often co-localized with elastin and collagen [31][32][33] and binds to collagen in vitro [34]. A distribution of A1M at various interfaces between the cells of the body and the ambient environment (blood/tissue, air/tissue, intestinal lumen/villi), as well as at the interface between maternal blood and fetal tissues in placenta [35,36], is consistent with a protective role of A1M in vivo (see below).…”

Tissue Distribution of the Lipocalin Alpha-1 Microglobulin in the Developing Human Fetus

“…Significant synthesis of ␣ 1 m has not been demonstrated in adult human tissues other than liver and possibly pancreas (Itoh et al 1996;Berggård et al 1998). Therefore, as discussed above for the intestinal mucosa, it is likely that the presence of ␣ 1 m at some of the other tissue sites, notably the perivascular extracellular matrix in adults (Odum and Nielsen 1994;Berggård et al 1998;Santin and Cannas 1999), as well as in fetal tissue (current study) results from transport and deposition of hepatocyte-synthesized ␣ 1 m. The transport pathways for such deposition remain to be clarified but may involve certain high molecular weight ␣ 1 m complexes (notably those with IgA, albumin, and some proteinase inhibitors; Berggård et al 1997). In this context, it is interesting to note that there is considerable variability among tissues in their relative composition of high molecular weight complexes (Berggård et al 1998).…”

Redox properties of the lipocalin α1-microglobulin: Reduction of cytochrome c, hemoglobin, and free iron

“…α 1 m is found in blood and in connective tissue in most organs and is most abundant at interfaces between the cells of the body and the environment, such as in lungs, intestine, kidneys and placenta [13][14][15][16]. α 1 m has immunosuppressive properties, such as inhibition of antigeninduced proliferation of human peripheral lymphocytes, migration and chemotaxis of granulocytes [17,18], IL-2 production by T-cells [19], and activation of the mononuclear cells [20].…”