neutrophil migration/adhesion/margination

[guarana]

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can somebody help me? i'm currently separated from my beloved robbins book....
and i can't get straight who is required for what--selectin helps the neutrophils migrate to site of inflammation, but i can never remember which other mediators are important for what....ICAM, LFA, wtf?

what is the molecule that signals the neutrophil to marginate?

any help/clarification would be greatly appreciated!

 

[divinemsm]

E-selectins on the endothelium bind to mucin adhesion molecules on neutrophils : this is brief = " rolling "

various chemokines ( IL8,C5a bind to neutrohils/phagocytes and cause conformational change in the integrin molecules to increase affinity of neutrophil for the adhesion molecules on the endothelium = " activation "

the integrins on the neutrophil and the ICAMS ( adhesion molecules ) on the endothelium interact and stabilize adhesion of the neutrophil to the endothelial cell= " arrest and adhesion "

the neutrophil/phagocyte goes into the tissues using psuedopodia=migration

* IL8, C5a, leukotriene B4, are chemoattractants for neutrophils

 

[pillowhead]

can somebody help me? i'm currently separated from my beloved robbins book....
and i can't get straight who is required for what--selectin helps the neutrophils migrate to site of inflammation, but i can never remember which other mediators are important for what....ICAM, LFA, wtf?

what is the molecule that signals the neutrophil to marginate?

any help/clarification would be greatly appreciated!

IL-8 and C5a are chemotactic factors for neutrophils. Rolling/loose interactions are mediated by selectins (specifically L-selectins are on the neutrophils while P- and E-selectins are on the endothelial cells). Tight adhesions are mediated by integrins. LFA1 is an integrin on the neutrophil surface that binds to ICAMS and VCAMS expressed on the endothelium. Diapedesis and migration to the site of injury is just the neutrophil following chemotactic gradients.

That's it in a nutshell...hope that helps (and hope it's right!).

 

[pillowhead]

divinemsm...looks like we were responding at the same time!

 

[guarana]

cool, that definitely helps. its one of those things i've memorized more than once and forgotten more than once....

so there are no specific molecules that mediate diapedisis, it's just a continuation of the migration?

thanks so much for the help!!

 

[HiddenTruth]

PEe selectin on endoth cells bind to oligosacch on leukocytes (sialyl lewis eX)

l (L) selectins on neutrophills bind to gly-cam 1 on endoth cells

platelet endoth cell adh molecule 1 (PECAM-1) are on endoth cells and leukocytes, and they mediate diapedesis (transmigration across endothelium)

Someone mentioned IL-8 as increasing adh mol synth--are u sure about this?You probably are right, some reason I always distinguised this guy as only acting as a chemoattractant.

yea, this stuff is a hoe to remember--
remember IL-1 and TNF participate in increasing adh mol synth but not as chemoattractants. While LTB4 and C5a do both. And, I know IL-8 is chmoattr for sure, not sure about increasing adh mold synth.
Don't forget steroids inhibit adh mol synth on neutrophills (neutrophillia), while endotoxin do the opposite. And while corticosteroids increase neutr, they decrease lymphocytes and eosino, via apoptosis.

 

[guarana]

PEe selectin on endoth cells bind to oligosacch on leukocytes (sialyl lewis eX)

l (L) selectins on neutrophills bind to gly-cam 1 on endoth cells

platelet endoth cell adh molecule 1 (PECAM-1) are on endoth cells and leukocytes, and they mediate diapedesis (transmigration across endothelium)

Someone mentioned IL-8 as increasing adh mol synth--are u sure about this?You probably are right, some reason I always distinguised this guy as only acting as a chemoattractant.

yea, this stuff is a hoe to remember--
remember IL-1 and TNF participate in increasing adh mol synth but not as chemoattractants. While LTB4 and C5a do both. And, I know IL-8 is chmoattr for sure, not sure about increasing adh mold synth.
Don't forget steroids inhibit adh mol synth on neutrophills (neutrophillia), while endotoxin do the opposite. And while corticosteroids increase neutr, they decrease lymphocytes and eosino, via apoptosis.

thanks hidden, that helps even more!

 

[Scottish Chap]

This was my post-doc. research area, so I can help a little; most of the responses above are correct, and they're all telling you a little bit of the story. It's important to differentiate between early (therefore acute) and late (chronic) inflammatory events. The later events involve gene expression (VCAM, ICAM etc.). In terms of your question: p-selectin is what first 'grabs' hold of passing leukocytes in the ciculation, allowing them to roll along the endothelium (actually, I was just measuring this real time in vivo today). This p-selectin is stored in specialzed granules inside endothelial cells (Weibel-Palade bodies; also contain vWF), and also inside alpha-granules in platelets. This p-selectin is released by a number of stimuli including hypoxia, thrombin, histamine, and complement exposure. The endothelial p-selectin is released by exocytosis and most of it end up on the luminal side of the endothelium. It sticks to receptors on leukocytes. A little ends up in the blood stream (soluble p-selectin and its function is still debated). Well, you didn't ask for a very detailed answer of how the process starts, but you sure got one!

 

[guarana]

that's awesome. a real expert! lucky day 🙂
thanks--
guarana