Significance of mononuclear phagocytes in IgA nephropathy

Abstract

To clarify the significance of mononuclear phagocytes in IgA nephropathy, renal biopsied materials from 45 patients with the disease were examined by the indirect immunoperoxidase method using anti-human monoclonal antibodies and by ultrastructural peroxidase (PO) cytochemistry. The monoclonal antibodies were FMC32, S-100 (alpha), My4, and LeuM5 for detection of mononuclear phagocytes and HLA-DR for Ia antigens. Mesangial hypercellularity in IgA nephropathy was divided into three grades. The number of monocyte/macrophages per glomerulus differed significantly among the grade of mesangial hypercellularity. In the capillary lumen, monocytes were more numerous in the group with slight mesangial hypercellularity. By contrast, macrophages were often found in the Bowman's space and mesangial area of the glomeruli in the advanced group. In the renal interstitium, the number of monocyte/macrophages per 100 interstitial cells differed significantly among the degree of interstitial damage, and they were observed mainly around sclerotic glomeruli. Ultrastructural PO cytochemistry revealed infiltration of monocytes, exudate macrophages, and/or PO-negative macrophages. Clinicopathological study showed a relationship between the number of monocyte/macrophages per glomerulus and the number of glomerular crescents and the degree of proteinuria. The constancy of the percentage of exudate macrophages and polymorphonuclear leukocytes were observed irrespective of the grade of mesangial hypercellularity. On the other hand, the increasing percentage of PO-negative macrophages and decreasing percentage of monocytes were observed over the grade. These results suggest that mononuclear phagocytes might play an important role in the pathogenesis of mesangial hypercellularity, and irreversible glomerular damage and interstitial tissue injury in IgA nephropathy.

Suppression of mesangial proliferative glomerulonephritis development in rats by inhibitors of cAMP phosphodiesterase isozymes types III and IV.

“…We used the potent PDE-III antagonist lixazinone (LX) together with rolipram (RP), an antagonist of PDE-IV, which by itself has little anti-mitogenic activity in MC but which enhances effects of PDE-III antagonists (9). More importantly, PDE-IV antagonist can also suppress ROM formation in glomeruli (16) and in MC (17) and ROM generated by infiltrating monocytes (18,31). Generated ROM may not only inflict injury to glomerular cells and capillary wall in vivo (18,19), but at lower subtoxic concentration may stimulate MCP-1 synthesis (21) in MC and possibly activate MAPK (32).…”

Fcα receptor I activation induces leukocyte recruitment and promotes aggravation of glomerulonephritis through the FcRγ adaptor

“…The initial phase of disease involves IgA-IC-containing components such as abnormal glycosylated polymeric IgA1 and soluble FcRc-less FcaRI [16,17]. The progression in severe cases can be associated with mononuclear cell infiltration in the kidney, leading to glomerular damage and interstitial tissue injury [18][19][20][21]. The involvement of transmembrane FcaRI signaling by IgA-IC in the pathogenesis of GN remains unclear.…”

Inhibitory ITAM Signaling by FcαRI-FcRγ Chain Controls Multiple Activating Responses and Prevents Renal Inflammation

“…Disease progression is characterized by a persistent inflammatory response that causes irreversible renal glomerulosclerosis and tubulointerstitial fibrosis eventually leading to ESRD. Human nephropathies are frequently associated with leukocyte infiltration, a feature of poor prognosis (2)(3)(4)(5)(6). Mice that spontaneously develop lupus-like renal inflammation are protected when they lack FcR␥, the common subunit of activating Fc receptors on myeloid cells (7).…”