Neutrophil Beta‐2 Microglobulin: an Inflammatory Mediator

Abstract

Beta-2 microglobulin (beta 2m) constitutes the light invariant chain of HLA class I antigen, and is a constituent of mobilizable compartments of neutrophils. Two forms of beta 2m exist: native beta 2m and proteolytically modified beta 2m (Des-Lys58-beta 2m), which shows alpha mobility in crossed radioimmuno-electrophoresis. The modification of native beta 2m can be executed by membrane-associated activity of mononuclear cells, and Des-Lys58-beta 2m augments the production of interleukin 2. In this study we present evidence that human neutrophils contain native beta 2m in specific granules, secretory vesicles, and plasma membrane. Beta 2m was released in the native form from neutrophils in response to stimulation with chemotactic stimuli and phorbol ester. The results of experiments designed to study the modification of native beta 2m by neutrophils indicated that neutrophils do not participate in the proteolysis of beta 2m. However, we demonstrated that native beta 2m following degranulation may be transformed to Des-Lys58-beta 2m by lymphocytes. We suggest that neutrophil beta 2m following exocytosis may be transformed to Des-Lys58-beta 2m, acting as an extracellular messenger between granulocytes and lymphocytes in the inflammatory focus.

FcRn: an IgG receptor on phagocytes with a novel role in phagocytosis

“…1,4 Unlike the classical leukocyte Fc␥Rs, which are the only IgG receptors described so far on PMNs, we found FcRn to be exclusively localized in intracellular compartments in freshly isolated PMNs. The intracellular localization to both azurophilic and specific granules corroborates previous studies showing the presence of ␤2M in specific granules and secretory vesicles in PMNs 29 and with studies documenting FcRn expression within human macrophages 12 and in human and porcine monocytes. 12,30 Our data are also in agreement with previous work showing that degranulation mediates translocation of FcRn from intracellular compartments to the cell surface on monocytes.…”

Rheumatoid factors from patients with rheumatoid arthritis react with Des-Lys58 -β2m, modified β2-microglobulin

“…Findings presented here are of considerable interest, since they do not directly support the idea that proteolylic degradation products of fi^m occurring as the result of endogenous complement activation and generation of CIs [9] could be ihe natural pathway for production of an endogenous antigen capable of stimulating RF production. This is apparent since most RF showed strongest reaeliviiy for the native /^m anti not the intermediate Lys^^ specific neutrophil granules and may exert profound biologic effects on granule component function on degranulation of polymorphonuclear leucocytes (PMN) [19]. The modification of ;m to Des-Lys'^-^^m can be initiated by cell membraneassociated activities and can then augment IL-2 production, thereby possibly acting as an intercellular messenger between PMN and lymphocytes in inflammatory states [19].…”

Modified Human Beta 2‐Microglobulin (desLys58) Displays Decreased Affinity for the Heavy Chain of MHC Class I and Induces Nitric Oxide Production and Apoptosis

“….................................................................................................................................................................. Interferon-c is secreted by antigen-activated T cells, which were shown previously to convert b2m to db2m [20]. In addition, the granules of neutrophils contain substantial amounts of b2m [38,39], which also might be an important source for proteolytically converted db2m in the microenvironment at the site of immune reactivity. In the inflammatory environment, high levels of db2m might dampen immune reactivity by affecting the survival of antigen-presenting cells (such as macrophages and dendritic cells), thus being capable of fine-tuning the immune response.…”