Cross‐linking of neutrophil CD11b results in rapid cell surface expression of molecules required for antigen presentation and T‐cell activation

Abstract

Summary Recent studies suggest that neutrophils may play a role in antigen presentation. In support of this hypothesis it has been shown that these cells appear to contain cytoplasmic stores of molecules required for this function, i.e. major histocompatibility complex class II (DR) antigen, CD80 and CD86. In this study we have considered a mechanism for the translocation of these preformed molecules onto the cell surface which does not require active synthesis. Cross‐linking of the Mac‐1 molecule (CD18 + CD11b) was shown to result in rapid cell surface expression of CD80, CD86 and DR antigen on the surface of normal human peripheral blood neutrophils. A distinct subpopulation (approximately 20%) of neutrophils appeared to be enlarged and were found to express significantly elevated levels of these molecules on the cell surface following cross‐linking of CD11b when compared with control cells. The level of expression of CD80, CD86 and DR antigen on these large cells was comparable to, and in some cases greater than, the levels found expressed on the surface of monocytes obtained from the same donors. In addition, these cytoplasmic molecules were shown by confocal laser microscopy and by immunoelectron microscopy to be located within secretory vesicles. Following rapid translocation onto the cell surface, CD80 and CD86 appeared to be colocalized within large clusters reminiscent of the supramolecular antigen clusters previously found on conventional antigen‐presenting cells. These findings therefore lend further support for the hypothesis that neutrophils may have a role to play in antigen presentation and/or T‐cell activation.

Inefficiency of C3H/HeN Mice to Control Chlamydial Lung Infection Correlates with Downregulation of Neutrophil Activation During the Late Stage of Infection

“…In a pregnant mouse model with C. psittaci serotype І infection and an anti-neutrophil MoAb (RB6-8C5), the lack of neutrophils led to a substantial decrease in the number of macrophages and T lymphocytes in the liver of mice (6). Indeed, using confocal microscopy and immunoelectron microscopy Gavin P, et al provided evidences that CD80, CD86 and MHC class II antigen are colocalized within neutrophil secretory vesicles, and the cross-linking of neutrophils CD11b was required for the translocation of these molecules from pre-existing cytoplasmic stores onto the cell surface (31). Therefore, during the late stage of infection, the down-regulation of CD11b expression on neutrophils in C3H mice might attenuate the antigen-presenting function of neutrophils, which may be another mechanism of the high susceptibility of C3H mice to C. trachomatis infection.…”

Airway Inflammation and Upregulation of β2 Mac‐1 Integrin Expression on Circulating Leukocytes of Female Ragpickers in India

“…Neutrophils are among the first cells to respond to inflammation, and circulating platelets help them in this endeavor, first by self-activation, then by mediating integrin expression on the neutrophil surface through release of P-selectin from alpha granules and adenosine tri-and diphosphate from dense bodies 18) . Besides antibacterial activity, Mac-1 integrin molecules mediate antigen presentation and/or T-cell activation 19) . Overexpression of CD11b/CD18 on leukocyte surfaces in ragpickers, therefore, possibly underscores stimulation of immune defense to combat pathogenic microorganisms in their working environment 16) .…”

Neutrophil-Mediated Inhibition of Proinflammatory Cytokine Responses

“…In addition, these cells have a more elaborate role in the innate defense against pathogens. Both in vitro and in vivo studies have shown that neutrophils are capable of Ag presentation by MHC class II complexes (5)(6)(7) and are able to express the costimulatory molecules CD80 and CD86 (8), which are relevant for induction of T cell proliferation (5, 7). Activated neutrophils have been shown to secrete cytokines such as IL-1, IL-1Ra, IL-6, IL-8, IL-12, IL-10, TNF-a, IFN-g, and PGE 2 (9)(10)(11)(12)(13).…”