Article Text
Abstract
Background: Neutrophils may exacerbate intestinal inflammatory diseases through secretion of proteolytic enzymes and reactive oxygen and nitrogen intermediates.
Aims: To define the mechanisms involved in neutrophil infiltration into the non-steroidal anti-inflammatory disease inflamed intestine to develop strategies to regulate this process.
Methods: The small intestinal epithelium of (15 mg/kg) indomethacin treated rats was examined for cytokine mRNA. The kinetics of neutrophil accumulation into the gastrointestinal tract (including lumen contents) of inflamed rats was determined using radiolabelled (111In) neutrophils injected intravenously followed by a three hour migration period. To determine which adhesion molecules were critical for migration, rats were also injected with function blocking monoclonal antibodies to the β2 (CD11/CD18) integrins.
Results: Interleukin 1β, interleukin 1 receptor II, tumour necrosis factor α, and monocyte inflammatory peptide 2 but not monocyte chemoattractant protein 1 mRNA were detected in the epithelium within hours of indomethacin injection. Neutrophils were detectable in the small intestine and intestinal lumen by six hours and continued to accumulate until 48 hours post indomethacin injection. Neutrophil accumulation in the intestine was essentially blocked by anti-CD18, and partially blocked by either anti-CD11a or CD11b antibody treatment. Migration into the intestinal lumen was reduced by anti-CD11b.
Conclusions: The small intestinal epithelium acts as one source of cytokines with properties important in the recruitment of neutrophils. In turn, neutrophil migration into the indomethacin inflamed small intestine is mediated by CD11a/CD18 and CD11b/CD18.
- neutrophil
- β2 integrin
- chemokine
- migration
- indomethacin
- IEC, intestinal epithelial cells
- IL-1β, interleukin 1β
- IL-1RII, interleukin 1 receptor II
- MIP-2, monocyte inflammatory peptide 2
- mAb, monoclonal antibody
- MPO, myeloperoxidase
- PBS, phosphate buffered saline
- RT-PCR, reverse transcription-polymerase chain reaction
- TNF-α, tumour necrosis factor α
- rbc, red blood cells
- LFA-1, lymphocyte function associated molecule 1
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- IEC, intestinal epithelial cells
- IL-1β, interleukin 1β
- IL-1RII, interleukin 1 receptor II
- MIP-2, monocyte inflammatory peptide 2
- mAb, monoclonal antibody
- MPO, myeloperoxidase
- PBS, phosphate buffered saline
- RT-PCR, reverse transcription-polymerase chain reaction
- TNF-α, tumour necrosis factor α
- rbc, red blood cells
- LFA-1, lymphocyte function associated molecule 1