Author/Editor     Kotnik, Vladimir
Title     C5a modulation of human neutrophil granulocyte apoptosis
Translated title     Pomen odlomka C5a pri apoptozi človeških nevtrofilnih granulocitov
Type     članek
Source     Med Razgl
Vol. and No.     Letnik 43, št. Suppl 5
Publication year     2004
Volume     str. 21-8
Language     eng
Abstract     Apoptosis is a natural way of elimination of cells, which are no longer needed. Mature granulocytes are terminally differentiated and undergo apoptosis permanently. Reduced cell death of granulocytes is an important mechanism for cell accumulation in inflammation. Several molecules can induce or prevent apoptosis of granulocytes. The role of CSa, one of the most powerful chemoattractants, which activates granulocytes via C5aR, was investigated. The annexin binding technique discriminating translocation of membrane phosphatidilserine molecules was used to detect early phases of apoptosis. We found a dose dependent modulation of human blood neutrophil granulocytes apoptosis. Low doses of C5a (1 x 10-11 to 1 x 10-9 M) were apoptogenic, but high doses (1 x 10-8 and 1 x 10-7) prevented granulocytes from apoptosis. We speculate that C5a activates C5aR, which is a 7-TMS receptor connected to the system of G-proteins. G-proteins are activators of phosphatidilinositol and responsible for generation of diacylglicerol. These molecules are connected with activation of caspases and these with apoptosis. Activation of CSaR employing C5a is one of the possible pathways for induction of apoptosis in human granulocytes. High doses of C5a allow neutrophils to live longer because they are needed for the destruction of the pathogen; low doses drive cells to apoptosis, preventing accumulation of destructing cells at the site of a healing lesion.
Summary     Apoptoza je eden od načinov, s katerimi organizem uravnava število svojih celic. Zreli nevtrofilni granulociti so dokončno oblikovane cefice in se ne morejo več deliti. Po določenem času odmrejo zaradi apoptoze. Med vnetjem se mora število granulocitov povečati. Takšno povečanje je lahko posledica zmanjšanega umiranja. Na pojav apoptoze vplivajo različni dejavniki, ki uravnavajo homeostazo organizma, med njimi tudi komplementni sistem. Proučevali smo vlogo C5a pri apoptozi človeških krvnih nevtrofilnih granulocitov. Z metodo vezanja aneksina smo merili translokacijo membranskega fosfatidilserina, ki je ena od sprememb, značilnih za zgodnje faze apoptoze. Ugotovili smo, da C5a modulira apoptozo nevtrofilcev odvisno od odmerka. Majhni odmerki C5a (1 x 10-11 do 1 x 10-9 M) apotozo pospešujejo, veliki odmerki (1 x 10-8 in 1 x 10-7) pa jo zavirajo. Aktivacija C5aR s C5a je ena od možnih poti, ki vodijo nevtrofilne granulocite v apoptozo. C5aR aktivira proteine G, ti pa aktivirajo kaspaze, ki sprožijo apoptozo. Veliki odmerki C5a omogočijo kopičenje granulocitov na vnetišču in jim obenem podaljšajo življenje, saj morajo ti med vnetjem uničiti velike množice patogenov. Majhni odmerki granulocite vodijo v apoptozo ter tako preprečijo njihovo kopičenje na mestu vnetja in nepotrebno škodo, ki bi nastala ob njihovi degranulaciji.
Descriptors     NEUTROPHILS
APOPTOSIS
COMPLEMENT 5A
ANNEXIN V
PHOSPHATIDYLSERINES
FLOW CYTOMETRY
LUPUS ERYTHEMATOSUS, SYSTEMIC