We report the identification and characterization of a new ischemia/reperfusion-inducible protein (IRIP), which belongs to the SUA5/YrdC/YciO protein family. IRIP cDNA was isolated in a differential display analysis of an ischemia/reperfusion-treated kidney RNA sample. Mouse IRIP mRNA was expressed in all tissues tested, the highest level being in the testis, secretory, and endocrine organs. Besides ischemia/reperfusion, endotoxemia also activated the expression of IRIP in the liver, lung, and spleen. The transporter regulator RS1 was identified as an IRIP-interacting protein in yeast two-hybrid screening. The interaction between IRIP and RS1 was further confirmed in coimmunoprecipitation assays. A possible role of IRIP in regulating transporter activity was subsequently investigated. IRIP overexpression inhibited endogenous 1-methyl-4-phenylpyridinium (MPP ؉ ) uptake activity in HeLa cells. The activities of exogenous organic cation transporters (OCT2 and OCT3), organic anion transporter (OAT1), and monoamine transporters were also inhibited by IRIP. Conversely, inhibition of IRIP expression by small interfering RNA or antisense RNA increased MPP ؉ uptake. We measured transport kinetics of OCT2-mediated uptake and demonstrated that IRIP overexpression significantly decreased V max but did not affect K m . On the basis of these results, we propose that IRIP regulates the activity of a variety of transporters under normal and pathological conditions.

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Staphylococcal protein A is a bacterial cell wall product that binds human immunoglobulin G and thereby interferes with opsonization and phagocytosis of Staphylococcus aureus by neutrophils. Phagocytic cells are also responsive to various non-immunoglobulin lymphocyte mediators. We utilized the detection of a newly recognized mediator, a neutrophil migration inhibition factor from T-lymphocytes (NIF-T), to show that aggregates of staphylococcal protein A and immunoglobulins G could inhibit the responsiveness of neutrophils to NIF-T. That such aggregates may alter the responsiveness of neutrophils to lymphocyte mediators that amplify or modulate phagocytic functions may have important pathogenetic implications in staphylococcal infection.

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