Mauro Perretti#

Short laudatio by Roderick John Flower#

Mauro Perretti is a 50-year-old Italian pharmacologist, now working in the UK, who has made an international impact for his work on anti-inflammatory drugs and mechanisms of inflammatory resolution.

Since 1987 Perretti has co-authored almost 200 peer review publications, 40 symposium publications and book chapters, and 150 abstracts. He has delivered over 40 invited key note and other lectures at meetings around the world including Europe, Canada, the US, Brazil, Finland and Denmark as well as over 30 invited seminars within the UK. He has supervised some 18 PhD students examined almost 20 PhD or MD students and set up collaborations all over the world with laboratories including those within the UK, in the US, Italy and Hungary. He has held consultancies for 8 pharmaceutical companies and he himself holds some 7 patents or applications. During the last decade he has raised over £l0M in research grant income. Even though he is only just over half way through his career, he holds a personal chair in the William Harvey Research Institute, Bart’s and the London Medical School, Queen Mary College, London-one of the top 10% institutions in the UK (government figures).

Perretti’s early interests were in cytokines but he soon developed an interest in anti-inflammatory drugs and the process of inflammatory resolution. Many of his publications deal with the glucocor-ticoid-regulated anti-inflammatory protein annexin A1 (Anx-A1; aka lipocortin). One of his most important early observations as a fully independent scientist described the mechanism whereby endogenous Anx-A1 was rapidly mobilised from neutrophils when they became attached to endothelial cells. He has continued to develop aspects of this discovery throughout his career demonstrating (for example) the importance of this mechanism in the control of leukocyte adherence in murine postcapillaiy venules, the role of the protease PR3 in terminating Anx-A1 action and the relevance of this to Wegener's granulomatasis, a disorder associated with excessive neutrophil activation.

To discover the mechanism through which Anx-Al brought about its striking biological effects Perretti launched a new investigation focusing on the potential role of the formyl peptide (FPR) receptor family. His first foray into this field was a joint paper with his colleague C.N Serhan (Boston, USA) and resulted in another paper in Nature Medicine that highlighted the role of the lipoxin A4 receptor (ALX; FPR-Ll) as the mechanism through which the annexin protein exerted its effects. He pursued this lead showing the importance of different members of the FPR family in inhibition of neutrophil function. In a new departure, working together with a new appointee, Perretti demonstrated that in addition to its potent action on the innate immune system, Anx-A1 also played a key role in the adaptive immune system, controlling T cell activation and differentiation, thus initiating another important strand of research into this pathway. This was reviewed in Ref 10, one of 3 reviews on various aspects of innate and adaptive immune response, Nature journals have invited Perrerti to co-author during the last 5 years.

Whilst his main interest has been in is in this area, Perretti has pioneered other important fields. Two examples: firstly, the notion that melanocortin receptors are important in regulating inflammation and that this provides an explanation for the anti-inflammatory effects of ACTH and associated peptides independent of their effect on the adrenal gland and secondly, the development of NO-donating glucocorticoids. These are a novel series of drugs that, whilst retaining their full potency have reduced side effects. Both these fields - as well as others he has initiated, are still vigorously pursued here under his direction.

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