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Updated: Aug 21, 2026
A Microphysiological System to Study Leukocyte-Endothelial Cell Interaction during Inflammation
Published on: December 9, 2021
Reduced leukocyte-endothelial cell interactions in the inflamed microcirculation of macrophage migration inhibitory
Julia L Gregory1, Michelle T Leech, John R David
1Centre for Inflammatory Diseases, Monash University, Victoria, Australia.
Objective:
Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine with established roles in a range of inflammatory conditions. However, it is not known whether MIF influences inflammation via the direct promotion of leukocyte-endothelial cell interactions. Therefore, the aim of these experiments was to investigate the ability of MIF to regulate leukocyte-endothelial cell interactions in the inflamed microvasculature.
Methods:
Intravital microscopy was used to examine postcapillary venules in the cremaster muscle and synovium of wild-type and MIF(-/-) mice. Leukocyte-endothelial cell interactions (rolling, adhesion, emigration) were compared under a range of inflammatory conditions.
Results:
In cremasteric postcapillary venules of MIF(-/-) mice, lipopolysaccharide (LPS)-induced leukocyte rolling, adhesion, and emigration were significantly reduced relative to that in wild-type mice. Similar responses were observed in response to tumor necrosis factor alpha and histamine. Examination of the synovial microvasculature following exposure to carrageenan revealed that leukocyte rolling and adhesion in synovial postcapillary venules and leukocyte entry into the joint space were also reduced significantly in MIF(-/-) mice. In each of these models, the level of P-selectin-dependent rolling was reduced in MIF(-/-) mice. Despite this, no difference in P-selectin expression was observed following LPS treatment. However, microvascular shear forces were elevated in MIF(-/-) mice, raising a possible mechanism to explain the reduced interactions in these animals.
Conclusion:
MIF(-/-) mice consistently displayed a reduction in P-selectin-dependent rolling, suggesting that MIF exerts proinflammatory effects, in part, via the promotion of P-selectin-mediated rolling. Together, these data indicate that MIF promotes interactions between leukocytes and endothelial cells, thereby enhancing the entry of leukocytes into sites of inflammation.
Insights
Macrophage migration inhibitory factor (MIF) reduces leukocyte interactions with blood vessels during inflammation. MIF deficiency in mice decreased leukocyte rolling, adhesion, and emigration, indicating MIF promotes inflammatory cell recruitment.
Area of Science:
- Immunology
- Cell Biology
- Vascular Biology
Background:
- Macrophage migration inhibitory factor (MIF) is a key proinflammatory cytokine.
- MIF's role in directly promoting leukocyte-endothelial cell interactions in inflammation is not well understood.
Purpose of the Study:
- To investigate the role of MIF in regulating leukocyte-endothelial cell interactions.
- To determine if MIF influences leukocyte recruitment to inflamed microvasculature.
Main Methods:
- Intravital microscopy was employed to study postcapillary venules in mouse cremaster muscle and synovium.
- Leukocyte-endothelial cell interactions (rolling, adhesion, emigration) were compared between wild-type and MIF-deficient (MIF(-/-)) mice under inflammatory conditions induced by LPS, TNF-alpha, histamine, and carrageenan.
Main Results:
- MIF(-/-) mice exhibited significantly reduced LPS-induced leukocyte rolling, adhesion, and emigration in cremasteric venules compared to wild-type mice.
- Similar reductions in leukocyte rolling and adhesion were observed in the synovial microvasculature of MIF(-/-) mice following carrageenan exposure.
- P-selectin-dependent rolling was decreased in MIF(-/-) mice, although P-selectin expression levels did not differ. Elevated microvascular shear forces in MIF(-/-) mice were noted.
Conclusions:
- MIF plays a significant role in promoting leukocyte-endothelial cell interactions during inflammation.
- MIF contributes to leukocyte recruitment by enhancing P-selectin-mediated rolling, thereby facilitating leukocyte entry into inflammatory sites.
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