PMID- 10653607
OWN - NLM
STAT- MEDLINE
DCOM- 20000210
LR  - 20131121
IS  - 0021-9541 (Print)
IS  - 0021-9541 (Linking)
VI  - 182
IP  - 3
DP  - 2000 Mar
TI  - Nitric oxide induces dose-dependent CA(2+) transients and causes temporal 
      morphological hyperpolarization in human neutrophils.
PG  - 402-13
AB  - We exposed adherent neutrophils to the nitric oxide (NO)-radical donors 
      S-nitroso-N-acetylpenicillamine (SNAP), S-nitrosoglutathione (GSNO), and sodium 
      nitroprusside (SNP) to study the role of NO in morphology and Ca(2+) signaling. 
      Parallel to video imaging of cell morphology and migration in neutrophils, 
      changes in intracellular free Ca(2+) ([Ca(2+)](i)) were assessed by ratio imaging 
      of Fura-2. NO induced a rapid and persistent morphological hyperpolarization 
      followed by migrational arrest that usually lasted throughout the 10-min 
      experiments. Addition of 0.5-800 microM SNAP caused concentration-dependent 
      elevation of [Ca(2+)](i) with an optimal effect at 50 microM. This was probably 
      induced by NO itself, because no change in [Ca(2+)](i) was observed after 
      treatment with NO donor byproducts, i.e. D-penicillamine, glutathione, or 
      potassium cyanide. Increasing doses of SNAP (>/=200 microM) attenuated the Ca(2+) 
      response to the soluble chemotactic stimulus 
      formyl-methionyl-leucyl-phenylalanine (fMLP), and both NO- and fMLP-induced 
      Ca(2+) transients were abolished at 800 microM SNAP or more. In kinetic studies 
      of fluorescently labeled actin cytoskeleton, NO markedly reduced the F-actin 
      content and profoundly increased cell area. Immunoblotting to investigate the 
      formation of nitrotyrosine residues in cells exposed to NO donors did not imply 
      nitrosylation, nor could we mimic the effects of NO with the cell permeant form 
      of cGMP, i.e., 8-Br-cGMP. Hence these processes were probably not the principal 
      NO targets. In summary, NO donors initially increased neutrophil morphological 
      alterations, presumably due to an increase in [Ca(2+)](i), and thereafter 
      inhibited such shape changes. Our observations demonstrate that the effects of NO 
      donors are important for regulation of cellular signaling, i.e., Ca(2+) 
      homeostasis, and also affect cell migration, e.g., through effects on F-actin 
      turnover. Our results are discussed in relation to the complex mechanisms that 
      govern basic cell shape changes, required for migration.
CI  - Copyright 2000 Wiley-Liss, Inc.
FAU - Loitto, V M
AU  - Loitto VM
AD  - Department of Medical Microbiology, Faculty of Health Sciences, Linkoping 
      University, Linkoping, Sweden. veslo@ihm.liu.se
FAU - Nilsson, H
AU  - Nilsson H
FAU - Sundqvist, T
AU  - Sundqvist T
FAU - Magnusson, K E
AU  - Magnusson KE
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Actins)
RN  - 0 (Indicators and Reagents)
RN  - 0 (Nitric Oxide Donors)
RN  - 0 (S-nitro-N-acetylpenicillamine)
RN  - 169D1260KM (Nitroprusside)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 3604-79-3 (3-nitrotyrosine)
RN  - 42HK56048U (Tyrosine)
RN  - GNN1DV99GX (Penicillamine)
RN  - H2D2X058MU (Cyclic GMP)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Actins/metabolism
MH  - Calcium/*metabolism
MH  - Calcium Signaling/*physiology
MH  - Cell Adhesion/drug effects/immunology
MH  - Cell Movement/drug effects/immunology
MH  - Cell Size/drug effects
MH  - Cyclic GMP/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Homeostasis/drug effects/physiology
MH  - Humans
MH  - Indicators and Reagents/pharmacology
MH  - Neutrophils/*cytology/*metabolism
MH  - Nitric Oxide/*metabolism
MH  - Nitric Oxide Donors/pharmacology
MH  - Nitroprusside/pharmacology
MH  - Penicillamine/analogs & derivatives/pharmacology
MH  - Tyrosine/analogs & derivatives/metabolism
EDAT- 2000/02/01 00:00
MHDA- 2000/02/01 00:01
CRDT- 2000/02/01 00:00
PHST- 2000/02/01 00:00 [pubmed]
PHST- 2000/02/01 00:01 [medline]
PHST- 2000/02/01 00:00 [entrez]
AID - 10.1002/(SICI)1097-4652(200003)182:3<402::AID-JCP11>3.0.CO;2-D [pii]
AID - 10.1002/(SICI)1097-4652(200003)182:3<402::AID-JCP11>3.0.CO;2-D [doi]
PST - ppublish
SO  - J Cell Physiol. 2000 Mar;182(3):402-13. doi: 
      10.1002/(SICI)1097-4652(200003)182:3<402::AID-JCP11>3.0.CO;2-D.