negative regulation of leukocyte cell-cell adhesion

Definition

Target type: biologicalprocess

Any process that stops, prevents or reduces the frequency, rate or extent of leukocyte cell-cell adhesion. [GO_REF:0000058, GOC:BHF, GOC:rl, GOC:TermGenie, PMID:21106532]

Negative regulation of leukocyte cell-cell adhesion is a crucial process that modulates the interaction of leukocytes with other cells, including endothelial cells, other leukocytes, and target cells. This intricate process involves a complex interplay of molecular mechanisms that fine-tune the recruitment, migration, and activation of leukocytes at sites of inflammation or injury. Key players in this regulation include adhesion molecules, chemokines, and signaling pathways.

Adhesion molecules, such as selectins, integrins, and immunoglobulin superfamily members, mediate the initial tethering and rolling of leukocytes on the endothelium. Negative regulation occurs through downregulation of these molecules' expression or their affinity for their ligands. This downregulation can be triggered by various mechanisms, including shedding of adhesion molecules from the cell surface, inactivation of adhesion molecules through phosphorylation or other post-translational modifications, and competition for binding sites by soluble counter-receptors.

Chemokines, small chemoattractant cytokines, play a vital role in leukocyte migration by forming gradients that guide leukocytes towards inflammation sites. Negative regulation of chemokine signaling can occur through various mechanisms, including downregulation of chemokine receptors, production of chemokine antagonists, and desensitization of intracellular signaling pathways.

Signaling pathways, such as the PI3K/Akt pathway, mediate the activation of leukocytes and the regulation of adhesion molecule expression. Negative regulation of these pathways can involve the activation of phosphatases that dephosphorylate key signaling molecules, the production of inhibitory proteins, and the activation of feedback loops that suppress signaling.

In addition to these molecular mechanisms, negative regulation of leukocyte cell-cell adhesion can also involve the recruitment of regulatory cells, such as regulatory T cells, that suppress the activation and migration of other leukocytes.

Overall, negative regulation of leukocyte cell-cell adhesion is a tightly controlled process that ensures the appropriate balance between leukocyte recruitment and activation, preventing excessive inflammation and tissue damage. This intricate process involves multiple levels of regulation, including the modulation of adhesion molecule expression, chemokine signaling, and intracellular signaling pathways.'
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Proteins (4)

Compounds (413)