PMID- 8652817
OWN - NLM
STAT- MEDLINE
DCOM- 19960731
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 87
IP  - 12
DP  - 1996 Jun 15
TI  - Continuous activation and deactivation of integrin CD11b/CD18 during de novo 
      expression enables rolling neutrophils to immobilize on platelets.
PG  - 5040-50
AB  - In an in vitro flow model, unstimulated neutrophils rolled steadily over a 
      surface coated with platelets, until superfusion of the chemotactic peptide 
      formyl-methionyl-leucyl-phenylalanine (fMLP) caused a dose-dependent (10(-11) to 
      10(-7) mol/L) transition from rolling to stationary attachment in seconds, 
      followed more slowly by neutrophil shape change and spreading on the surface, 
      However, at low concentrations of Ca2+ and Mg2+ (0.1 mmol/L and 0.05 mmol/L, 
      respectively, rather than physiologic 1 mmol/L and 0.5 mmol/L), neutrophils first 
      halted but then started to roll again and to detach from the surface over 5 to 10 
      minutes. At the low cation concentration, stopping was largely inhibited by 
      antibodies to the neutrophil integrins CD18 or CD11b, but not CD11a. When 
      neutrophils were pretreated with antibodies to CD11b or CD18 in 1 mmol/L Ca2+ 0.5 
      mmol/L Mg2+, stopping was not prevented but delayed. However, if antibodies were 
      also included with the superfused fMLP, stopping was inhibited, and detachment 
      followed. This indicates that CD11b/CD18 was newly expressed during shape change 
      and mediated the second phase of neutrophil immobilization and spreading in a 
      cation-dependent manner. Prestimulated neutrophils also bound to platelets and 
      spread, but immobilization was blocked if they were perfused with antibody to 
      CD18 or CD11b or with low Ca2+ and Mg2+. Examining the cation-dependence further, 
      it was evident that the presence of Mg2+ was essential for integrin-mediated 
      adhesion and that the Mg2+ concentration determined whether immobilization could 
      be maintained or was transient. Continuous superfusion of fMLP was also essential 
      for maintenance of stable adhesion and spreading. Thus, activation of 
      constitutive CD11b/CD18 rapidly and reversibly converted rolling to stationary 
      attachment, whereas maintenance of adhesion and neutrophil spreading required 
      continual expression of additional CD11b/CD18 that was only functional at 
      physiologic Mg2+. Continual activation and deactivation of CD11b/CD18 during de 
      novo expression could mediate immobilization and onward migration of neutrophils 
      in vivo, and activated platelets appear capable of supporting this process as 
      well as endothelial cells.
FAU - Sheikh, S
AU  - Sheikh S
AD  - Department of Physiology, The Medical School, The University of Birmingham, 
      Birmingham, UK.
FAU - Nash, G B
AU  - Nash GB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (CD18 Antigens)
RN  - 0 (Macrophage-1 Antigen)
RN  - 0 (P-Selectin)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - I38ZP9992A (Magnesium)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Blood Platelets/*cytology
MH  - CD18 Antigens/*physiology
MH  - Calcium/physiology
MH  - Cell Adhesion
MH  - Cells, Cultured
MH  - Chemotaxis, Leukocyte/*physiology
MH  - Humans
MH  - Macrophage-1 Antigen/*physiology
MH  - Magnesium/physiology
MH  - N-Formylmethionine Leucyl-Phenylalanine/pharmacology
MH  - Neutrophils/*cytology/drug effects/metabolism
MH  - P-Selectin/physiology
MH  - Stress, Mechanical
MH  - Thrombosis/physiopathology
EDAT- 1996/06/15 00:00
MHDA- 1996/06/15 00:01
CRDT- 1996/06/15 00:00
PHST- 1996/06/15 00:00 [pubmed]
PHST- 1996/06/15 00:01 [medline]
PHST- 1996/06/15 00:00 [entrez]
AID - S0006-4971(20)61203-4 [pii]
PST - ppublish
SO  - Blood. 1996 Jun 15;87(12):5040-50.