Modulating influence of chemotactic factor-induced cell adhesiveness on granulocyte function

Area of Science:

• Immunology
• Cell Biology
• Biochemistry

Background:

• The role of adhesion in regulating polymorphonuclear leukocyte (PMN) locomotion and accumulation is not fully understood.
• N-formyl peptides are known chemoattractants for PMNs, but their effect at higher concentrations is complex.

Purpose of the Study:

• To investigate the impact of N-formyl-methionyl-leucyl-phenylalanine (f-Met-Leu-Phe) concentration on human PMN adhesion and motility.
• To elucidate the mechanism behind high-dose inhibition of PMN chemotaxis.

Main Methods:

• Human PMNs were resuspended in heat-inactivated plasma and exposed to varying concentrations of f-Met-Leu-Phe.
• Cell motility was assessed by measuring random and chemotactic movement.
• Cell adherence to Petri dishes was quantified.
• Phase-contrast microscopy was used to observe cell morphology.
• Hexose monophosphate pathway activity and lysosomal enzyme release were measured.

Main Results:

• PMN chemotaxis was maximal at 1-10 nM f-Met-Leu-Phe but decreased significantly at concentrations above 100 nM.
• Increased f-Met-Leu-Phe concentrations led to heightened PMN adherence, with maximal adhesion at >10 nM.
• Cells exposed to high f-Met-Leu-Phe concentrations became flattened and immobilized, exhibiting reduced random and chemotactic motility.
• This hyperadhesiveness correlated strongly with increased hexose monophosphate pathway activity and lysosomal enzyme release.
• PMN ingestion rates were not depressed by high f-Met-Leu-Phe concentrations, indicating selective functional changes.

Conclusions:

• High-dose inhibition of PMN chemotaxis by N-formyl peptides is a result of increased cell adhesiveness, termed 'chemotactic deactivation'.
• This increased adhesion mechanism can lead to PMN trapping at inflammatory sites.
• Impaired PMN emigration due to this phenomenon may occur in conditions such as septicemia.