Macrophage Biology in Human Granulomatous Skin Inflammation.

Cutaneous granulomatoses represent a heterogeneous group of diseases, which are defined by macrophage infiltration in the skin. Skin granuloma can be formed in the context of infectious and non-infectious conditions. Recent technological advances have deepened our understanding of the pathophysiology of granulomatous skin inflammation, and they provide novel insights into human tissue macrophage biology at the site of ongoing disease. Here, we discuss findings on macrophage immune function and metabolism derived from three prototypic cutaneous granulomatoses: granuloma annulare, sarcoidosis, and leprosy.

Novel noninvasive marker of regression of clear cell renal cell carcinoma (ccRCC).

OBJECTIVE: Analyzing protein kinase C (PKC) alpha, iota, and zeta as well as levels of Mxi-2 and Vim3 in regressive clear cell renal carcinomas (ccRCCs) and urine samples. MATERIAL AND METHODS: Fresh samples of ccRCCs (predominantly pT1a/b) with different degrees of regression (<10%, 30%, 50%, and 70%) vs normal renal tissue and oncocytomas were studied by Western blot, using antibodies of different PKC isoforms. Urine samples from these tumors were analyzed by ELISA (PKC isoforms, Mxi-2, and Vim3). RESULTS: With increasing degree of regression beyond 10%, nuclear Mxi-2 and Vim3 were highly overexpressed in fresh tumor samples. In urine samples, Vim3 was significantly overexpressed in oncocytoma and downregulated in RCCs with 70% regression. Western blot analysis shows that PKC alpha and iota levels were significantly increased in fresh tumor tissue samples (tumors with 30% regression). PKC zeta was expressed in normal kidney and significantly increased in oncocytoma but not found in ccRCCs. In patients' urines, Mxi-2 was significantly reduced (regression > 50%), while PKC isoform alpha was significantly increased by advanced regression rate. PKC iota in patients' urine was overexpressed in oncocytoma and reduced in all ccRCC urines. CONCLUSION: Tumor regression in ccRCC tissue shows strong nuclear overexpression of Mxi-2, Vim3, and PKC alpha and iota. In respective urines, PKC alpha was overexpressed; PKC iota was decreased. Mxi-2 and Vim3 decreased with increasing regression rates. These reagents could serve as noninvasive ccRCC markers for regression.