title: Na+/H+ exchange and pH regulation in the control of neutrophil chemokinesis and chemotaxis.
abstract: Large proton fluxes accompany cell migration, but their precise role remains unclear. We studied pH regulation during the course of chemokinesis and chemotaxis in human neutrophils stimulated by attractant peptides. Activation of cell motility by chemoattractants was accompanied by a marked increase in metabolic acid generation, attributable to energy consumption by the contractile machinery and to stimulation of the NADPH oxidase and the ancillary hexose monophosphate shunt. Despite the increase in acid production, the cytosol underwent a sizable alkalinization, caused by acceleration of Na(+)/H(+) exchange. The development of the alkalinization mirrored the increase in the rate of cell migration, suggesting a causal relationship. However, elimination of Na(+)/H(+) exchange by omission of external Na(+) or by addition of potent inhibitors was without effect on either chemokinesis or chemotaxis, provided the cytosolic pH remained near neutrality. At more acidic levels, cell motility was progressively inhibited. These observations suggest that Na(+)/H(+) exchange plays a permissive role in cell motility but is not required for the initiation or development of the migratory response. Chemokinesis also was found to be exquisitely sensitive to extracellular acidification. This property may account for the inability of neutrophils to access abscesses and solid tumors that have been reported to have inordinately low pH.
authors: Cell Biology Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors: Hisayoshi
authors: H
authors: Hayashi
authors: Orit
authors: O
authors: Aharonovitz
authors: R Todd
authors: RT
authors: Alexander
authors: Nicolas
authors: N
authors: Touret
authors: Wendy
authors: W
authors: Furuya
authors: John
authors: J
authors: Orlowski
authors: Sergio
authors: S
authors: Grinstein
mesh_terms: D000143:Acids / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D027682:Cation Transport Proteins / Q000187:drug effects / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism*; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D045604:Extracellular Fluid / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006859:Hydrogen / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008856:Microscopy, Fluorescence; D008857:Microscopy, Interference; D019255:NADPH Oxidases / Q000187:drug effects / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000143:Acids; D027682:Cation Transport Proteins; D018925:Chemokines; D004791:Enzyme Inhibitors; C490998:SLC9A1 protein, human; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; D006859:Hydrogen; D012964:Sodium; D019255:NADPH Oxidases