PMID- 18768887 OWN - NLM STAT- MEDLINE DCOM- 20081118 LR - 20190516 IS - 1550-6606 (Electronic) IS - 0022-1767 (Linking) VI - 181 IP - 6 DP - 2008 Sep 15 TI - Hydrogen sulfide augments neutrophil migration through enhancement of adhesion molecule expression and prevention of CXCR2 internalization: role of ATP-sensitive potassium channels. PG - 4287-98 AB - In this study, we have addressed the role of H(2)S in modulating neutrophil migration in either innate (LPS-challenged naive mice) or adaptive (methylated BSA (mBSA)-challenged immunized mice) immune responses. Treatment of mice with H(2)S synthesis inhibitors, dl-propargylglycine (PAG) or beta-cyanoalanine, reduced neutrophil migration induced by LPS or methylated BSA (mBSA) into the peritoneal cavity and by mBSA into the femur/tibial joint of immunized mice. This effect was associated with decreased leukocyte rolling, adhesion, and P-selectin and ICAM-1 expression on endothelium. Predictably, treatment of animals with the H(2)S donors, NaHS or Lawesson's reagent, enhanced these parameters. Moreover, the NaHS enhancement of neutrophil migration was not observed in ICAM-1-deficient mice. Neither PAG nor NaHS treatment changed LPS-induced CD18 expression on neutrophils, nor did the LPS- and mBSA-induced release of neutrophil chemoattractant mediators TNF-alpha, keratinocyte-derived chemokine, and LTB(4). Furthermore, in vitro MIP-2-induced neutrophil chemotaxis was inhibited by PAG and enhanced by NaHS treatments. Accordingly, MIP-2-induced CXCR2 internalization was enhanced by PAG and inhibited by NaHS treatments. Moreover, NaHS prevented MIP-2-induced CXCR2 desensitization. The PAG and NaHS effects correlated, respectively, with the enhancement and inhibition of MIP-2-induced G protein-coupled receptor kinase 2 expression. The effects of NaHS on neutrophil migration both in vivo and in vitro, together with CXCR2 internalization and G protein-coupled receptor kinase 2 expression were prevented by the ATP-sensitive potassium (K(ATP)(+)) channel blocker, glybenclamide. Conversely, diazoxide, a K(ATP)(+) channel opener, increased neutrophil migration in vivo. Together, our data suggest that during the inflammatory response, H(2)S augments neutrophil adhesion and locomotion, by a mechanism dependent on K(ATP)(+) channels. FAU - Dal-Secco, Daniela AU - Dal-Secco D AD - Department of Pharmacology, School of Medicine of Ribeirao Preto, Ribeirao Preto, Brazil. FAU - Cunha, Thiago M AU - Cunha TM FAU - Freitas, Andressa AU - Freitas A FAU - Alves-Filho, Jose Carlos AU - Alves-Filho JC FAU - Souto, Fabricio O AU - Souto FO FAU - Fukada, Sandra Y AU - Fukada SY FAU - Grespan, Renata AU - Grespan R FAU - Alencar, Nylane M N AU - Alencar NM FAU - Neto, Alberto F AU - Neto AF FAU - Rossi, Marcos A AU - Rossi MA FAU - Ferreira, Sergio H AU - Ferreira SH FAU - Hothersall, John S AU - Hothersall JS FAU - Cunha, Fernando Q AU - Cunha FQ LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Adjuvants, Immunologic) RN - 0 (Cell Adhesion Molecules) RN - 0 (KATP Channels) RN - 0 (Lipopolysaccharides) RN - 0 (Receptors, Interleukin-8B) RN - 27432CM55Q (Serum Albumin, Bovine) RN - YY9FVM7NSN (Hydrogen Sulfide) SB - IM MH - Adjuvants, Immunologic/biosynthesis/*pharmacology MH - Animals MH - Cattle MH - Cell Adhesion Molecules/*biosynthesis/deficiency/genetics MH - Endocytosis/drug effects/*immunology MH - Gene Expression Regulation/drug effects/*immunology MH - Hydrogen Sulfide/metabolism/*pharmacology MH - Immunity, Innate/drug effects/genetics MH - KATP Channels/*physiology MH - Lipopolysaccharides/pharmacology MH - Male MH - Methylation/drug effects MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Neutrophil Infiltration/drug effects/*immunology MH - Receptors, Interleukin-8B/*antagonists & inhibitors/metabolism MH - Serum Albumin, Bovine/administration & dosage/immunology/metabolism EDAT- 2008/09/05 09:00 MHDA- 2008/11/19 09:00 CRDT- 2008/09/05 09:00 PHST- 2008/09/05 09:00 [pubmed] PHST- 2008/11/19 09:00 [medline] PHST- 2008/09/05 09:00 [entrez] AID - 181/6/4287 [pii] AID - 10.4049/jimmunol.181.6.4287 [doi] PST - ppublish SO - J Immunol. 2008 Sep 15;181(6):4287-98. doi: 10.4049/jimmunol.181.6.4287.