Interactions between haptoglobin and phagocytes

Haptoglobin is an important serum protein which undergoes upregulation in the setting of inflammation such as infection and trauma. Recently it has been demonstrated that this group of serum proteins influence phagocytic cells (monocytes and granulocytes) in their specific function. During the tenure of this project it was clearly demonstrated that elevated haptoglobin levels reduce migration of phagocytes towards a chemoatractant molecule. Similarly it was demonstrated that the phagocytic as well as the bactericidal activity are reduced in presence of elevated haptoglobin levels. On the search for a cell surface haptoglobin receptor or binding protein on peripheral blood leukocytes TIP49a named also RUVBL1 or Pontin52 has been identified. Surprisingly this protein which has already been characterised by other research groups was found to contribute to the formation of the nuclear spindle in the mitotic process of myeloid progenitor cells. It was found associated with a-tubulin in all phases of the mitotic process. This observation seems of importance as the protein, which is involved in several cell biological processes, might serve as a pharmacotherapeutic target in rapidly proliferating cells such as malignant tumors and leukemia. One new protein could be partially identified by screening a human leukocyte cDNA library. According to the data available so far the protein is expressed in every tissue of the human body with higher expression in the placenta, heart, and skeletal muscle. The biological function of this protein is as yet not defined. In addition a third new protein has been identified in its primary structure and in part in its biological function. This protein was named secretagogin as it is expressed solely in hormone secreting cells and a subgroup of neurons. In respect of this protein several data exist that it might serve as a relevant serum marker protein in certain clinical settings as stroke. In summary this project has achieved remarkable progress in 3 aspects: A) it has given further insight in the interaction of haptoglobin with phagocytes, B) a new biologically important function was identified for TIP49a, the contribution to mitotic spindle formation. C) New proteins have been partially or completely identified. During the tenure of these studies international collaborations were exquisite in order to achieve all the data.