PMID- 22768936
OWN - NLM
STAT- MEDLINE
DCOM- 20121009
LR  - 20220414
IS  - 1542-0086 (Electronic)
IS  - 0006-3495 (Print)
IS  - 0006-3495 (Linking)
VI  - 102
IP  - 8
DP  - 2012 Apr 18
TI  - Shear-induced resistance to neutrophil activation via the formyl peptide 
      receptor.
PG  - 1804-14
LID - 10.1016/j.bpj.2012.03.053 [doi]
AB  - The application of fluid shear stress on leukocytes is critical for physiological 
      functions including initial adhesion to the endothelium, the formation of 
      pseudopods, and migration into tissues. The formyl peptide receptor (FPR) on 
      neutrophils, which binds to formyl-methionyl-leucyl-phenylalanine (fMLP) and 
      plays a role in neutrophil chemotaxis, has been implicated as a fluid shear 
      stress sensor that controls pseudopod formation. The role of shear forces on 
      earlier indicators of neutrophil activation, such as L-selectin shedding and 
      alpha(M)beta(2) integrin activation, remains unclear. Here, human neutrophils exposed to 
      uniform shear stress (0.1-4.0 dyn/cm(2)) in a cone-and-plate viscometer for 1-120 
      min showed a significant reduction in both alpha(M)beta(2) integrin activation and 
      L-selectin shedding after stimulation with 0.5 nM of fMLP. Neutrophil resistance 
      to activation was directly linked to fluid shear stress, as the response 
      increased in a shear stress force- and time-dependent manner. Significant 
      shear-induced loss of FPR surface expression on neutrophils was observed, and 
      high-resolution confocal microscopy revealed FPR internalized within neutrophils. 
      These results suggest that physiological shear forces alter neutrophil activation 
      via FPR by reducing L-selectin shedding and alpha(M)beta(2) integrin activation in the 
      presence of soluble ligand.
CI  - Copyright (c) 2012 Biophysical Society. Published by Elsevier Inc. All rights 
      reserved.
FAU - Mitchell, Michael J
AU  - Mitchell MJ
AD  - Department of Biomedical Engineering, Cornell University, Ithaca, New York, USA.
FAU - King, Michael R
AU  - King MR
LA  - eng
GR  - HL018128/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Biophys J
JT  - Biophysical journal
JID - 0370626
RN  - 0 (Interleukin-8)
RN  - 0 (Macrophage-1 Antigen)
RN  - 0 (Protease Inhibitors)
RN  - 0 (Receptors, Formyl Peptide)
RN  - 126880-86-2 (L-Selectin)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
SB  - IM
MH  - Biomechanical Phenomena
MH  - Dose-Response Relationship, Drug
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Interleukin-8/pharmacology
MH  - L-Selectin/metabolism
MH  - Macrophage-1 Antigen/metabolism
MH  - N-Formylmethionine Leucyl-Phenylalanine/pharmacology
MH  - *Neutrophil Activation/drug effects
MH  - Neutrophils/drug effects/immunology/metabolism
MH  - Protease Inhibitors/pharmacology
MH  - Protein Transport/drug effects
MH  - Receptors, Formyl Peptide/*metabolism
MH  - *Shear Strength/drug effects
MH  - Stress, Mechanical
MH  - Time Factors
PMC - PMC3328724
EDAT- 2012/07/10 06:00
MHDA- 2012/10/10 06:00
PMCR- 2013/04/18
CRDT- 2012/07/10 06:00
PHST- 2011/09/14 00:00 [received]
PHST- 2012/03/20 00:00 [revised]
PHST- 2012/03/22 00:00 [accepted]
PHST- 2012/07/10 06:00 [entrez]
PHST- 2012/07/10 06:00 [pubmed]
PHST- 2012/10/10 06:00 [medline]
PHST- 2013/04/18 00:00 [pmc-release]
AID - S0006-3495(12)00394-3 [pii]
AID - BPJ3779 [pii]
AID - 10.1016/j.bpj.2012.03.053 [doi]
PST - ppublish
SO  - Biophys J. 2012 Apr 18;102(8):1804-14. doi: 10.1016/j.bpj.2012.03.053.